Fasciclin-like arabinogalactan proteins(FLAs),a subclass of arabinogalactan proteins(AGPs),are usually involved in cell development in plants.To investigate the expression profiling as well
Gene expression profiling at early stages(0~2 DPA) of fiber development in Gossypium hirsutum identified a number of transcription factors which were down regulated in fiberless mutants relative to wild type controls...Gene expression profiling at early stages(0~2 DPA) of fiber development in Gossypium hirsutum identified a number of transcription factors which were down regulated in fiberless mutants relative to wild type controls and which could play a role in controlling early fiber development.Chief among these was GhMYB25,a Mixta-like MYB gene.Transgenic GhMYB25-silenced cotton展开更多
Objective: The effect of Chuanzhi Fang (ZGC) on the whole genome expression profile of RAW264.7 cells activated by lipopolysaccharide (LPS) was analyzed, and to explore the possible mechanism of action and core target...Objective: The effect of Chuanzhi Fang (ZGC) on the whole genome expression profile of RAW264.7 cells activated by lipopolysaccharide (LPS) was analyzed, and to explore the possible mechanism of action and core target of this formula on macrophage inflammatory injury at the overall level. Methods: A model of LPS-induced inflammation in RAW264.7 cells was constructed, and the effect of ZGC intervention on the genome-wide expression of inflammatory macrophages 3was examined by gene microarray technology, GO/KEGG enrichment analysis was performed for significantly differentially expressed genes among each group. Results: The results of genome-wide expression profiling microarray analysis showed that the ZGC intervention group upregulated the expression of 5 genes including C4bp and inhibited the expression of 22 genes including Mgat3, Psma6, and Siglecg relative to the LPS model group. KEGG signaling pathway analysis results showed that ZGC mainly acted through cytokine receptor interaction and the C-type lectin receptor signaling pathway. Conclusion: ZGC can interfere with the abnormal expression of 27 genes in inflammatory macrophages, and the related genes may exert corresponding anti-inflammatory effects by affecting cytokine receptor interactions, C-type lectin receptor signaling pathway, and TLR4/ NF-κB signaling pathway.展开更多
<i><span style="font-family:Verdana;"><i>Diabetes mellitus</i></span><i></i></i><span style="font-family:Verdana;"> is a chronic disease that i...<i><span style="font-family:Verdana;"><i>Diabetes mellitus</i></span><i></i></i><span style="font-family:Verdana;"> is a chronic disease that impacts the homeostasis of blood sugar levels caused by loss or defect of insulin-producing β-cells in the Islets of Langerhans.</span> <i><span color:black;"=""><span style="font-family:Verdana;"><i>Type 1 diabetes</i></span><i></i></span></i><span style="font-family:Verdana;"> (</span><i><i></i><i><span style="font-family:Verdana;">T1D</span></i><i></i></i><span style="font-family:Verdana;">)</span><i><span color:black;"=""> </span></i><span style="font-family:Verdana;">is caused by auto-immune mediated destruction of β-cells,</span> <span color:black;"=""><span style="font-family:Verdana;">whereas in </span><i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i></span><span style="font-family:Verdana;">, insulin is produced but used inefficiently.</span><span color:black;"=""> <i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i></span><span style="font-family:Verdana;"> accounts for 90% of people with diabetes worldwide (</span><i><i></i><i><span style="font-family:Verdana;">WHO</span></i><i></i></i><i> </i><span style="font-family:Verdana;">1999)</span><span style="font-family:Verdana;"> and is</span> <span style="font-family:Verdana;">the fastest increasing disease worldwide (</span><span style="font-family:Verdana;"><a href="https://diabetesatlas.org/en/" target="_blank">https://diabetesatlas.org/en/</a></span><span style="font-family:Verdana;">)</span><span color:black;"=""><span style="font-family:Verdana;">. For an improved understanding of the pathomechanism of diabetes, profound knowledge of pancreas organogenesis and the associated gene regulatory networks is required. Therefore, we dissected and profiled the pancreatic endodermal and non-endodermal compartment between the embryonic stages (E) 12.5 and E 15.5 when progenitor cells commit to their different pancreatic lineages. Our associated study mined the global mRNA expression profile to increase the understanding of the secondary transition, endodermal-non-endodermal tissue interaction, and diabetic-related gene regulation. Furthermore, we validated 635 regulated pancreatic genes using the publicly available </span><i><i></i><i><span style="font-family:Verdana;">GenePaint.org</span></i><span color:black;"=""><span style="font-family:Verdana;">, respective </span><i><span style="font-family:Verdana;">gp3.mpg.de</span></i></span><i></i></i></span><span style="font-family:Verdana;"> to evaluate genes associated with genetic variants in Single-nucleotide polymorphism (SNP) related to </span><i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i><span style="font-family:Verdana;">.</span>展开更多
[ Objective ] The aim of the research was to study the expression profile changes of genes involved in lipid metabolism pathway during liver regeneration in mice. [ Method] The CCI4 induced mouse model of liver regene...[ Objective ] The aim of the research was to study the expression profile changes of genes involved in lipid metabolism pathway during liver regeneration in mice. [ Method] The CCI4 induced mouse model of liver regeneration was established and the total RNA was isolated from liver tissue of mouse. Then the changes of genes involved in lipid metabolism pathway during different stages of liver regeneration were detected through micro-array chip gene technique and their specific functions were also analyzed. [ Result] Dudng the process of liver regeneration, the expression level of 98 genes involved in lipid metabolism pathway changed, which were divided into eight groups according to change trend. In the mass, the expression of genes was inhibited in the early stage and up-regulated in the late phase. And the gene expression associated with fatty acid synthesis pathway was mainly up-regulated while the catabolic pathway did not change significantly. Most of genes involved in bile acid synthesis pathway were suppressed before 4.5 d and up-regulated after 4.5 d or 7 d. [ Conclusion] During the process of liver regeneration, the genes associated with lipid metabolism are expressed in different trends, and this data should provide a specific range of genes for further studying the regulation effect of lipid metabolism related pathway on liver regeneration.展开更多
Objective: To study the genes expression profile differences in the peripheral blood between esophageal carcinoma patients and normal subjects using the gene chip technique and screen out the esophageal early concera...Objective: To study the genes expression profile differences in the peripheral blood between esophageal carcinoma patients and normal subjects using the gene chip technique and screen out the esophageal early conceration associated genes. Methods: The total RNA was extracted and purified in the peripheral blood obtained from the patients with esophageal carcinoma and normal subjects. The first strand of cDNA was synthesized through retro-transcription and labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with a piece of 4096 double dot human whole gene chip. The acquired image was analyzed by microarrav suite software using a digital computer, and the intensity of ttuorescence signal and its ratio were calculated. Results: A total of 92 genes were screened out and its expression difference was more than 2 times in the peripheral blood between the patients with esophageal carcinoma and normal subjects. Among these, the expression difference of 36 genes was more than 3 times. Two human urokinase plasminogen activator surface receptor (UPAR) genes, 80K-L protein gene, human protein tyrosine-phosphatase gent arid proto-oncogene protein mRNA were significantly up-regulated, while the collagen V type (α-2 gene was markedly down-regulated. Conclusion: 80K-L protein gene, tyrosinephophatase gene, proto-oncogene protein arid the collagen V type α-2 gene might be associated with the ontogenesis, development and its metastasis in the esophageal carcinoma. The UPAR gene may play important roles in the diagnosing the micrometastasis in the peripheral blood of esophageal carcinoma.展开更多
AIM: To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory (ES) product. METHODS: NIH-3T3, mouse fibroblast cells were treated with O. viverrini...AIM: To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory (ES) product. METHODS: NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA (cDNA) array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR. RESULTS: Among a total of 15 000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O.viverrini ES product, The expression level of signal transduction genes, pkC, pdgfra, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC,eps 8 and tgfβ3 1/4 which are the downstream signaling molecules of either epidermal growth factor (EGF) or transforming growth factor-β (TGF-β) showed statistical significance (P 〈 0.05).CONCLUSION: O. viverrini ES product stimulates the significant changes of gene expression in several functional categories and these mainly include transcripts related to cell proliferation. The TGF-β and EGF signal transduction pathways are indicated as the possible pathways of O. viverrini-driven cell proliferation.展开更多
AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differenti...AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.METHODS: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS: RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION: Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.展开更多
AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we...AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a lowand a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.展开更多
Objective: Ajoene, a major compound extracted from crashed garlic, has been shown to have antitumor, antimycotic, antimicrobial, antimutagenic functions in vivo or in vitro and treated as a potential antitumor drug. H...Objective: Ajoene, a major compound extracted from crashed garlic, has been shown to have antitumor, antimycotic, antimicrobial, antimutagenic functions in vivo or in vitro and treated as a potential antitumor drug. However, the molecular mechanisms underlying the tumor cytotoxicity of ajoene and even garlic substances are poorly defined. In the present study, we aimed to generate gene expression profiles of HL-60 cell treated by ajoene. Methods: A cDNA microarray presenting 2400 of genes amplified from human leukocyte cDNA library was constructed and the gene expression profiles of HL-60 cell induced by ajoene were generated. Results: After data analysis, 28 differentially expressed genes were identified and sequenced. These genes include 21 known genes and 7 ESTs. Most of the known genes are related to cell apoptosis, such as secretory granule (PRG1), beta-2 microglobulin (B2M), 16S ribosomal RNA gene and ribosomal protein S12. Several genes are related to cell differentiation, including the genes similar to H3 histone and ribosomal protein L31. Northern blot analysis was used to verify and quantify the expression of selected genes. Conclusion: Ajoene can induce HL-60 cell apoptosis significantly and may play a role in differentiation. cDNA microarray technology can be a valuable tool to gain insight into molecular events of pharmacological mechanism of herbal medicine.展开更多
Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,...Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,a genome-wide characterization of the CPP gene family has been absent in Camellia sinensis.In this study,we totally identified 7,8,and 8 non-redundant CsCPP genes in three published genomes,including Camellia sinensis var.assamica cv.Yunkang-10(CSA-YK10),Camellia sinensis var.sinensis cv.Biyun(CSS-BY)and Camellia sinensis var.sinensis cv.Shuchazao(CSS-SCZ).CPP proteins from tea tree and other plant species were classified into three groups,which were further divided into four subgroups based on phylogenetic relationships.Most CPP genes in the same subgroup had similar gene structures and conserved motifs.The cis-acting elements analysis indicated that CPP genes might be involved in plant growth,development and stress responses.Analysis of gene expression using qRT-PCR experiments validated that CPP genes exhibited different expression patterns across the examined tissues.All the genes were expressed differentially in a range of tissues,indicating that CPPs were involved in a range of developmental and physiological processes.This study has obtained new insights into the evolution and function of the CPP gene family in the growth and development of tea plants,and also provide candidate genes for further functional characterization in tea tree.展开更多
The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experi...The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.展开更多
The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened ou...The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 (4. 85 %) genes significantly differed between the ESCC with and without lymphatic metastasis (P〈0.05), of which 18(2.03 %)were upregulated and 25 (2.82 %) down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.展开更多
Sea cucumbers Apostichopus japonicus are one of the most important aquaculture species in China. Their normal body color is black to fi t their surroundings. Wild albinos are rare and hard to breed. To understand the ...Sea cucumbers Apostichopus japonicus are one of the most important aquaculture species in China. Their normal body color is black to fi t their surroundings. Wild albinos are rare and hard to breed. To understand the differences between albino and normal(control) sea cucumbers at the transcriptional level, we sequenced the transcriptomes in their body-wall tissues using RNA-Seq high-throughput sequencing. Approximately 4.876 million(M) and 4.884 M 200-nucleotide-long cDNA reads were produced in the cDNA libraries derived from the body walls of albino and control samples, respectively. A total of 9 561(46.89%) putative genes were identifi ed from among the RNA-Seq reads in both libraries. After fi ltering, 837 signifi cantly differentially regulated genes were identifi ed in the albino library compared with in the control library, and 3.6% of the differentially expressed genes(DEGs) were found to have changed those more than fi ve-fold. The expression levels of 10 DEGs were checked by real-time PCR and the results were in full accord with the RNA-Seq expression trends, although the amplitude of the differences in expression levels was lower in all cases. A series of pathways were signifi cantly enriched for the DEGs. These pathways were closely related to phagocytosis, the complement and coagulation cascades, apoptosis-related diseases, cytokine-cytokine receptor interaction, and cell adhesion. The differences in gene expression and enriched pathways between the albino and control sea cucumbers offer control targets for cultivating excellent albino A. japonicus strains in the future.展开更多
Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient wh...Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.展开更多
Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidat...Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.展开更多
Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p ...Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.展开更多
BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.Th...BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.展开更多
The SQUAMOSA promoter binding protein (SBP)-box genes encode a kind of plant-specific transcription factors (TFs) and play important roles in the regulation of plant development. In this study, a genome-wide chara...The SQUAMOSA promoter binding protein (SBP)-box genes encode a kind of plant-specific transcription factors (TFs) and play important roles in the regulation of plant development. In this study, a genome-wide characterization of this family was conducted in maize (Zea mays). Thirty-one SBP-box genes were identified to be distributed in nine chromosomes and 16 of them were complementary to the mature ZmmiR156 sequences. All the Z. mays SBP (ZmSBP) genes were classified into two clusters with eight subgroups according to the phylogenetic analysis of proteins, which were consistent with the pattern of exon-intron structures. The phylogenetic tree of the ZmSBP, Oryza sativa SBP-like (OsSPL) and Arabidopsis thaliana SBP-like (AtSPL) genes were constructed and all the SBP-box genes were divided into eight groups, which was the same as the classification of ZmSBP genes. The comparision of the expression profiles of all SBP-box genes in these three species indicated that most orthologous genes had similar expression patterns. The results from this study provided a basic understanding of the ZmSBP genes and might facilitate future researches for elucidating the SBP-box genes function in maize.展开更多
文摘Fasciclin-like arabinogalactan proteins(FLAs),a subclass of arabinogalactan proteins(AGPs),are usually involved in cell development in plants.To investigate the expression profiling as well
文摘Gene expression profiling at early stages(0~2 DPA) of fiber development in Gossypium hirsutum identified a number of transcription factors which were down regulated in fiberless mutants relative to wild type controls and which could play a role in controlling early fiber development.Chief among these was GhMYB25,a Mixta-like MYB gene.Transgenic GhMYB25-silenced cotton
基金Chinese Academy of Traditional Chinese Medicine Autonomous Topic Selection Project(No.ZZ2018017)Research Development Fund Project of the Medical Experimental Center of the Chinese Academy of Traditional Chinese Medicine(No.FZ2023003)。
文摘Objective: The effect of Chuanzhi Fang (ZGC) on the whole genome expression profile of RAW264.7 cells activated by lipopolysaccharide (LPS) was analyzed, and to explore the possible mechanism of action and core target of this formula on macrophage inflammatory injury at the overall level. Methods: A model of LPS-induced inflammation in RAW264.7 cells was constructed, and the effect of ZGC intervention on the genome-wide expression of inflammatory macrophages 3was examined by gene microarray technology, GO/KEGG enrichment analysis was performed for significantly differentially expressed genes among each group. Results: The results of genome-wide expression profiling microarray analysis showed that the ZGC intervention group upregulated the expression of 5 genes including C4bp and inhibited the expression of 22 genes including Mgat3, Psma6, and Siglecg relative to the LPS model group. KEGG signaling pathway analysis results showed that ZGC mainly acted through cytokine receptor interaction and the C-type lectin receptor signaling pathway. Conclusion: ZGC can interfere with the abnormal expression of 27 genes in inflammatory macrophages, and the related genes may exert corresponding anti-inflammatory effects by affecting cytokine receptor interactions, C-type lectin receptor signaling pathway, and TLR4/ NF-κB signaling pathway.
文摘<i><span style="font-family:Verdana;"><i>Diabetes mellitus</i></span><i></i></i><span style="font-family:Verdana;"> is a chronic disease that impacts the homeostasis of blood sugar levels caused by loss or defect of insulin-producing β-cells in the Islets of Langerhans.</span> <i><span color:black;"=""><span style="font-family:Verdana;"><i>Type 1 diabetes</i></span><i></i></span></i><span style="font-family:Verdana;"> (</span><i><i></i><i><span style="font-family:Verdana;">T1D</span></i><i></i></i><span style="font-family:Verdana;">)</span><i><span color:black;"=""> </span></i><span style="font-family:Verdana;">is caused by auto-immune mediated destruction of β-cells,</span> <span color:black;"=""><span style="font-family:Verdana;">whereas in </span><i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i></span><span style="font-family:Verdana;">, insulin is produced but used inefficiently.</span><span color:black;"=""> <i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i></span><span style="font-family:Verdana;"> accounts for 90% of people with diabetes worldwide (</span><i><i></i><i><span style="font-family:Verdana;">WHO</span></i><i></i></i><i> </i><span style="font-family:Verdana;">1999)</span><span style="font-family:Verdana;"> and is</span> <span style="font-family:Verdana;">the fastest increasing disease worldwide (</span><span style="font-family:Verdana;"><a href="https://diabetesatlas.org/en/" target="_blank">https://diabetesatlas.org/en/</a></span><span style="font-family:Verdana;">)</span><span color:black;"=""><span style="font-family:Verdana;">. For an improved understanding of the pathomechanism of diabetes, profound knowledge of pancreas organogenesis and the associated gene regulatory networks is required. Therefore, we dissected and profiled the pancreatic endodermal and non-endodermal compartment between the embryonic stages (E) 12.5 and E 15.5 when progenitor cells commit to their different pancreatic lineages. Our associated study mined the global mRNA expression profile to increase the understanding of the secondary transition, endodermal-non-endodermal tissue interaction, and diabetic-related gene regulation. Furthermore, we validated 635 regulated pancreatic genes using the publicly available </span><i><i></i><i><span style="font-family:Verdana;">GenePaint.org</span></i><span color:black;"=""><span style="font-family:Verdana;">, respective </span><i><span style="font-family:Verdana;">gp3.mpg.de</span></i></span><i></i></i></span><span style="font-family:Verdana;"> to evaluate genes associated with genetic variants in Single-nucleotide polymorphism (SNP) related to </span><i><i></i><i><span style="font-family:Verdana;">T2D</span></i><i></i></i><span style="font-family:Verdana;">.</span>
文摘[ Objective ] The aim of the research was to study the expression profile changes of genes involved in lipid metabolism pathway during liver regeneration in mice. [ Method] The CCI4 induced mouse model of liver regeneration was established and the total RNA was isolated from liver tissue of mouse. Then the changes of genes involved in lipid metabolism pathway during different stages of liver regeneration were detected through micro-array chip gene technique and their specific functions were also analyzed. [ Result] Dudng the process of liver regeneration, the expression level of 98 genes involved in lipid metabolism pathway changed, which were divided into eight groups according to change trend. In the mass, the expression of genes was inhibited in the early stage and up-regulated in the late phase. And the gene expression associated with fatty acid synthesis pathway was mainly up-regulated while the catabolic pathway did not change significantly. Most of genes involved in bile acid synthesis pathway were suppressed before 4.5 d and up-regulated after 4.5 d or 7 d. [ Conclusion] During the process of liver regeneration, the genes associated with lipid metabolism are expressed in different trends, and this data should provide a specific range of genes for further studying the regulation effect of lipid metabolism related pathway on liver regeneration.
基金This project was supported by a grant from the Zhejiang Medical and Health Science Foundation (No. 2002A023).
文摘Objective: To study the genes expression profile differences in the peripheral blood between esophageal carcinoma patients and normal subjects using the gene chip technique and screen out the esophageal early conceration associated genes. Methods: The total RNA was extracted and purified in the peripheral blood obtained from the patients with esophageal carcinoma and normal subjects. The first strand of cDNA was synthesized through retro-transcription and labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with a piece of 4096 double dot human whole gene chip. The acquired image was analyzed by microarrav suite software using a digital computer, and the intensity of ttuorescence signal and its ratio were calculated. Results: A total of 92 genes were screened out and its expression difference was more than 2 times in the peripheral blood between the patients with esophageal carcinoma and normal subjects. Among these, the expression difference of 36 genes was more than 3 times. Two human urokinase plasminogen activator surface receptor (UPAR) genes, 80K-L protein gene, human protein tyrosine-phosphatase gent arid proto-oncogene protein mRNA were significantly up-regulated, while the collagen V type (α-2 gene was markedly down-regulated. Conclusion: 80K-L protein gene, tyrosinephophatase gene, proto-oncogene protein arid the collagen V type α-2 gene might be associated with the ontogenesis, development and its metastasis in the esophageal carcinoma. The UPAR gene may play important roles in the diagnosing the micrometastasis in the peripheral blood of esophageal carcinoma.
基金the Thailand Research Fund, Grant No. TRG4880004 and the Grants of Khon Kaen University 2004 and 2006 Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan the Grant for Student of Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, 2003-2005
文摘AIM: To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory (ES) product. METHODS: NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA (cDNA) array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR. RESULTS: Among a total of 15 000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by O.viverrini ES product, The expression level of signal transduction genes, pkC, pdgfra, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC,eps 8 and tgfβ3 1/4 which are the downstream signaling molecules of either epidermal growth factor (EGF) or transforming growth factor-β (TGF-β) showed statistical significance (P 〈 0.05).CONCLUSION: O. viverrini ES product stimulates the significant changes of gene expression in several functional categories and these mainly include transcripts related to cell proliferation. The TGF-β and EGF signal transduction pathways are indicated as the possible pathways of O. viverrini-driven cell proliferation.
基金Supported by Contrat Universite Paul Sabatier,Toulouse,France,ASUPS 2000(N.Vaysse)AOL DRC Hopitaux de Toulouse 2001,(L.Buscail)Region Midi-Pyrenees(L.Buscail)H.Laurell was supported by a grant from European Community Plan 99 ECC QLG3-CT-1999-0908(C.Susini)The Agilent 2100 Bioanalyzer and the phosphoimager(Molecular Dynamics,Sunnyvale,CA,USA)were at the Transcriptome Platform,Toulouse Genopole,and at the molecular biology platform at the Institute Louis Bugnard,IFR31,Toulouse,France,respectively
文摘AIM: To compare gene expression profiles of pancreatic adenocarcinoma tissue specimens, human pancreatic and colon adenocarcinoma and leukemia cell lines and normal pancreas samples in order to distinguish differentially expressed genes and to validate the differential expression of a subset of genes by quantitative real-time RT-PCR (RT-QPCR) in endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) specimens.METHODS: Commercially dedicated cancer cDNA macroarrays (Atlas Human Cancer 1.2) containing 1176 genes were used. Different statistical approaches (hierarchical clustering, principal component analysis (PCA) and SAM) were used to analyze the expression data. RT-QPCR and immunohistochemical studies were used for validation of results.RESULTS: RT-QPCR validated the increased expression of LCN2 (lipocalin 2) and for the first time PLAT (tissue-type plasminogen activator or tPA) in malignant pancreas as compared with normal pancreas. Immunohistochemical analysis confirmed the increased expression of LCN2 protein localized in epithelial cells of ducts invaded by carcinoma. The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues, indicating that a sufficient amount of high quality RNA can be obtained with this technique.CONCLUSION: Expression profiling is a useful method to identify biomarkers and potential target genes. Molecular analysis of EUS-guided FNA samples in pancreatic cancer appears as a valuable strategy for the diagnosis of pancreatic adenocarcinomas.
基金Supported by the National 863 Program (SQ2009AA02-XK1482570 and 2006AA02A402)Beijing Municipal Committeeof Science and Technology (D0905001040631) Beijing Capi-tal Development Foundation of Health Bureau (2007-2051)
文摘AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47 296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a lowand a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.
文摘Objective: Ajoene, a major compound extracted from crashed garlic, has been shown to have antitumor, antimycotic, antimicrobial, antimutagenic functions in vivo or in vitro and treated as a potential antitumor drug. However, the molecular mechanisms underlying the tumor cytotoxicity of ajoene and even garlic substances are poorly defined. In the present study, we aimed to generate gene expression profiles of HL-60 cell treated by ajoene. Methods: A cDNA microarray presenting 2400 of genes amplified from human leukocyte cDNA library was constructed and the gene expression profiles of HL-60 cell induced by ajoene were generated. Results: After data analysis, 28 differentially expressed genes were identified and sequenced. These genes include 21 known genes and 7 ESTs. Most of the known genes are related to cell apoptosis, such as secretory granule (PRG1), beta-2 microglobulin (B2M), 16S ribosomal RNA gene and ribosomal protein S12. Several genes are related to cell differentiation, including the genes similar to H3 histone and ribosomal protein L31. Northern blot analysis was used to verify and quantify the expression of selected genes. Conclusion: Ajoene can induce HL-60 cell apoptosis significantly and may play a role in differentiation. cDNA microarray technology can be a valuable tool to gain insight into molecular events of pharmacological mechanism of herbal medicine.
文摘Cysteine-rich polycomb-like(CPP)is a small gene family in plants,which plays key role in plant development and stress response.Although CPP transcription factors have been characterized in several other plant species,a genome-wide characterization of the CPP gene family has been absent in Camellia sinensis.In this study,we totally identified 7,8,and 8 non-redundant CsCPP genes in three published genomes,including Camellia sinensis var.assamica cv.Yunkang-10(CSA-YK10),Camellia sinensis var.sinensis cv.Biyun(CSS-BY)and Camellia sinensis var.sinensis cv.Shuchazao(CSS-SCZ).CPP proteins from tea tree and other plant species were classified into three groups,which were further divided into four subgroups based on phylogenetic relationships.Most CPP genes in the same subgroup had similar gene structures and conserved motifs.The cis-acting elements analysis indicated that CPP genes might be involved in plant growth,development and stress responses.Analysis of gene expression using qRT-PCR experiments validated that CPP genes exhibited different expression patterns across the examined tissues.All the genes were expressed differentially in a range of tissues,indicating that CPPs were involved in a range of developmental and physiological processes.This study has obtained new insights into the evolution and function of the CPP gene family in the growth and development of tea plants,and also provide candidate genes for further functional characterization in tea tree.
文摘The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.
基金This project was supported by a grant of 2004 Henan Pro-vincial Science and Technology Key Program Foundation(No .0424410109)
文摘The differentially expressed genes between esophageal squamous cell carcinoma (ESCC) with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 (4. 85 %) genes significantly differed between the ESCC with and without lymphatic metastasis (P〈0.05), of which 18(2.03 %)were upregulated and 25 (2.82 %) down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.2012AA10A412)the National Natural Science Foundation of China(No.40976089)+1 种基金the National Key Technology Research and Development Program of China(No.2011BAD13B02)the National Oceanic Public Welfare Industry Special Scientifi c Research of China(No.201205023)
文摘Sea cucumbers Apostichopus japonicus are one of the most important aquaculture species in China. Their normal body color is black to fi t their surroundings. Wild albinos are rare and hard to breed. To understand the differences between albino and normal(control) sea cucumbers at the transcriptional level, we sequenced the transcriptomes in their body-wall tissues using RNA-Seq high-throughput sequencing. Approximately 4.876 million(M) and 4.884 M 200-nucleotide-long cDNA reads were produced in the cDNA libraries derived from the body walls of albino and control samples, respectively. A total of 9 561(46.89%) putative genes were identifi ed from among the RNA-Seq reads in both libraries. After fi ltering, 837 signifi cantly differentially regulated genes were identifi ed in the albino library compared with in the control library, and 3.6% of the differentially expressed genes(DEGs) were found to have changed those more than fi ve-fold. The expression levels of 10 DEGs were checked by real-time PCR and the results were in full accord with the RNA-Seq expression trends, although the amplitude of the differences in expression levels was lower in all cases. A series of pathways were signifi cantly enriched for the DEGs. These pathways were closely related to phagocytosis, the complement and coagulation cascades, apoptosis-related diseases, cytokine-cytokine receptor interaction, and cell adhesion. The differences in gene expression and enriched pathways between the albino and control sea cucumbers offer control targets for cultivating excellent albino A. japonicus strains in the future.
基金This work was supported by the NationalNatural Science Foundation of China(No.30070772)
文摘Objective: To establish gene expression profiles associated with malignant progression of ganglioglioma. Methods: The primary and two recurrent glioma specimens were collected intraoperatively from the same patient who experienced tumor transformation into anaplastic astrocytoma and glioblastoma multiform for the first and second recurrence respectively. Gene expression was assayed through cDNA array and bioinformatics analysis. Results: A total of 197 differentially expressed genes with differential ratio value more than 3 compared with normal brain tissue were obtained. Among 109 functionally denned genes, those associated with development ranked the first by frequency, followed by genes associated with metabolism, differentiation, signal transduction and so on. As a result of cluster analysis among 368 genes, eleven genes were up regulated with malignant progression, while six genes were down regulated. Conclusion: Gene expression profiles associated with malignant progression of glioma were successfully established, which provides a powerful tool for research on molecular mechanisms of malignant progression of gliomas.
基金This work was supported by the National Natural Science Foundation of China (No 30370904and No 30671258)the National High Technology Research and Development Program(863 project)of China (No 2006AA10Z121)the Program for New Century Excellent Talents in University(No NCET-07-0712)
文摘Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
基金European Sequencing and Genotyping Institutes(ESGI),Grant/Award Number:075491/Z/04,085906/Z/08/Z and 090532/Z/09/ZTel-Aviv University(TAU)。
文摘Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.
文摘Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.
基金National Key Research and Development Program of China,No.2021YFC2701704the National Clinical Medical Research Center for Geriatric Diseases,"Multicenter RCT"Research Project,No.NCRCG-PLAGH-20230010the Military Logistics Independent Research Project,No.2022HQZZ06.
文摘BACKGROUND Multiple myeloma(MM)is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow.The translocation,(t)(4;14),results in high-risk MM with limited treatment alternatives.Thus,there is an urgent need for identification and validation of potential treatments for this MM subtype.Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets.AIM To elucidate the molecular basis and search for potential effective drugs of t(4;14)MM subtype by employing a comprehensive approach.METHODS The transcriptional signature of t(4;14)MM was sourced from the Gene Expression Omnibus.Two datasets,GSE16558 and GSE116294,which included 17 and 15 t(4;14)MM bone marrow samples,and five and four normal bone marrow samples,respectively.After the differentially expressed genes were identified,the Cytohubba tool was used to screen for hub genes.Then,the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.Using the STRING database and Cytoscape,protein–protein interaction networks and core targets were identified.Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis,respectively.RESULTS In this study,a total of 258 differentially expressed genes with enriched functions in cancer pathways,namely cytokine receptor interactions,nuclear factor(NF)-κB signaling pathway,lipid metabolism,atherosclerosis,and Hippo signaling pathway,were identified.Ten hub genes(cd45,vcam1,ccl3,cd56,app,cd48,btk,ccr2,cybb,and cxcl12)were identified.Nine drugs,including ivermectin,deforolimus,and isoliquiritigenin,were predicted by the Connectivity Map database to have potential therapeutic effects on t(4;14)MM.In molecular docking,ivermectin showed strong binding affinity to all 10 identified targets,especially cd45 and cybb.Ivermectin inhibited t(4;14)MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro.Furthermore,ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14)MM cells.CONCLUSION Collectively,the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14)MM diagnosis and treatment,with ivermectin emerging as a potential therapeutic alternative.
基金support by the National Natural Science Foundation of China(31200911,31101576)the China Postdoctoral Science Foundation(20100471197,201104475)the Research Fund for the Doctoral Program of Higher Education of China(20110146120040)
文摘The SQUAMOSA promoter binding protein (SBP)-box genes encode a kind of plant-specific transcription factors (TFs) and play important roles in the regulation of plant development. In this study, a genome-wide characterization of this family was conducted in maize (Zea mays). Thirty-one SBP-box genes were identified to be distributed in nine chromosomes and 16 of them were complementary to the mature ZmmiR156 sequences. All the Z. mays SBP (ZmSBP) genes were classified into two clusters with eight subgroups according to the phylogenetic analysis of proteins, which were consistent with the pattern of exon-intron structures. The phylogenetic tree of the ZmSBP, Oryza sativa SBP-like (OsSPL) and Arabidopsis thaliana SBP-like (AtSPL) genes were constructed and all the SBP-box genes were divided into eight groups, which was the same as the classification of ZmSBP genes. The comparision of the expression profiles of all SBP-box genes in these three species indicated that most orthologous genes had similar expression patterns. The results from this study provided a basic understanding of the ZmSBP genes and might facilitate future researches for elucidating the SBP-box genes function in maize.