Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 pati...Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.展开更多
BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify ...BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.展开更多
Background： Cleidocranial dysplasia （CCD） is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of ...Background： Cleidocranial dysplasia （CCD） is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 （RUNX2）. Here, we report a sporadic Chinese case presenting typical symptoms of CCD. Methods： We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 ffameshift mutation： c.1111 dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. Results： RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. Conclusions： We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.展开更多
Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified ...Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified a gene(named GaPC) controlling petal coloration in Gossypium arboreum and following a heritable recessive epistatic genetic model. Petal coloration is controlled by a single dominant gene,GaPC. A loss-of-function mutation of GaPC leads to a recessive gene Gapc that masks the phenotype of other color genes and shows recessive epistatic interactions. Map-based cloning showed that GaPC encodes an R2R3-MYB transcription factor. A 4814-bp long terminal repeat retrotransposon insertion at the second exon led to GaPC loss of function and disabled petal coloration. GaPC controlled petal coloration by regulating the anthocyanin and flavone biosynthesis pathways. Expression of core genes in the phenylpropanoid and anthocyanin pathways was higher in colored than in white petals. Petal color was conferred by flavonoids and anthocyanins, with red and yellow petals rich in anthocyanin and flavonol glycosides, respectively. This study provides new insight on molecular mechanism of recessive epistasis,also has potential breeding value by engineering GaPC to develop colored petals or fibers for multifunctional utilization of cotton.展开更多
BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its ro...BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.展开更多
BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM...BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.展开更多
Objective:To study the correlation of Runt-related transcription factor gene 3 (RUNX3) expression in osteosarcoma tissue with cell proliferation and angiogenesis.Methods: A total of 80 patients with osteosarcoma who w...Objective:To study the correlation of Runt-related transcription factor gene 3 (RUNX3) expression in osteosarcoma tissue with cell proliferation and angiogenesis.Methods: A total of 80 patients with osteosarcoma who were treated in our hospital between February 2014 and February 2017 were collected, and the RUNX3 expression in osteosarcoma tissue and adjacent tissue were detected. According to the RUNX3 expression in tumor tissue, the patients were further divided into high RUNX3 expression group and low RUNX3 expression group, and the proliferation gene and angiogenesis gene expression were compared.Results:RUNX3, KISS-1 and RanBP9 mRNA expression in osteosarcoma tissue were significantly lower than those in adjacent tissue while VCP, Six1, S100A6, IF-1α, MMP-14, bFGF and Ang-2 mRNA expression were significantly higher than those in adjacent tissue;KISS-1 and RanBP9 mRNA expression in osteosarcoma tissue of high RUNX3 expression group were significantly higher than those of low RUNX3 expression group while VCP, Six1, S100A6, IF-1 , MMP-14, bFGF and Ang-2 mRNA expression were significantly lower than those of low RUNX3 expression group.Conclusions:The desease of RUNX3 expression in osteosarcoma tissue is one of the direct causes of increased tumor proliferation activity and strong angiogenesis.展开更多
To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rat...To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rats subjected to hypoxia. Immunohistochemistry demonstrated that Olig2 was expressed throughout the nuclei in the brain, and expression increased at 3 days following hypoxia and was higher than levels at 7 days following Ad5-Oligl transfection. Western blot revealed that Oligl and Olig2 expression increased in Oligl-transfected brain cells 3 days after hypoxia, but Oligl and Olig2 expression decreased at 7 days. These results indicate that Oligl overexpression enhances Olig2 expression in brain tissues of hypoxia rats.展开更多
Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related ...Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related genes responsible for seed specific triacylglycerols (TAGs) storage in oil plants. B3 type transcription factors, such as ABI3 and FUS3, are known to be involved in seed development, such as seed storage protein synthesis and maturation. Based on the recent whole genome sequence data of castor bean (Ricinus communis L.), putative WRI1 homologs (RcWRI1, RcWRI2) specifically expressed in castor bean seed have been identified by comparing organ specific expression profiles among seed development-related transcription factors, seed storage specific genes (Ricin, RcOleosin) and a set of FAS genes including genes for sucrose synthase (RcSUS2), biotin carboxyl carrier protein (a subunit of acetyl-CoA carboxylase, RcBCCP2) and ketoacyl-acyl carrier protein synthase (RcKAS1). Immunoreactive signals with WRI1, FUS3 and ABI5-related polypeptides were also detected in seed specifically, consistent with the expression profiles of seed development-related genes. The WRI1 binding consensus sites, [CnTnG](n)(7)[CG], designated as the AW-box, were found at the promoter region of RcBCCP2 and RcKAS1. Thus, RcWRI1 possibly play a pivotal role in seed specific TAGs storage during seed development by directly activating FAS -related genes.展开更多
Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both...Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both in ascomycete and basidiomycete fungi.We found that ZnFTFs were widely distributed in these fungal species,but there was more expansion of the ZnFTF class in Ascomycota than Basidiomycota.We identified 40 ZnFTFs in Ustilaginoidea virens,and demonstrated the involvement of UvZnFTF1 in vegetative growth,conidiation,pigment biosynthesis and pathogenicity.RNA-Seq analysis suggested that UvZnFTF1 may regulate different nutrient metabolism pathways,the production of secondary metabolites,and the expression of pathogen-host interaction genes and secreted protein-encodi ng genes.Analysis of the distributi on of differe nt fungal TFs in U.virens further dem on strated that UvZnFTFs make up a large TF family and may play essential biological roles in U.virens.展开更多
BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the ...BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.展开更多
AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation o...AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.展开更多
The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results...The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.展开更多
Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging...Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.展开更多
BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colo...BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer(CRC). Knockdown of VASH1 enhanced transforming growth factor-β1(TGF-β1)/Smad3 pathway activity and type Ⅰ/Ⅲ collagen production. Our previous findings suggest that ELL-associated factor 2(EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3(STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was upregulated in advanced CRC tissue compared to normal colorectal tissue. KaplanMeier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cellderived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.展开更多
文摘Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.
文摘BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.
基金This work was supported by a grant from the Natural Science Foundation of China （No. 81200762）.
文摘Background： Cleidocranial dysplasia （CCD） is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 （RUNX2）. Here, we report a sporadic Chinese case presenting typical symptoms of CCD. Methods： We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 ffameshift mutation： c.1111 dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. Results： RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. Conclusions： We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.
基金supported by the Fundamental Research Funds for the Central Universities(KYZZ2022003)Jiangsu Collaborative Innovation Center for Modern Crop Production project (No.10)。
文摘Although a few cases of genetic epistasis in plants have been reported, the combined analysis of genetically phenotypic segregation and the related molecular mechanism remains rarely studied. Here, we have identified a gene(named GaPC) controlling petal coloration in Gossypium arboreum and following a heritable recessive epistatic genetic model. Petal coloration is controlled by a single dominant gene,GaPC. A loss-of-function mutation of GaPC leads to a recessive gene Gapc that masks the phenotype of other color genes and shows recessive epistatic interactions. Map-based cloning showed that GaPC encodes an R2R3-MYB transcription factor. A 4814-bp long terminal repeat retrotransposon insertion at the second exon led to GaPC loss of function and disabled petal coloration. GaPC controlled petal coloration by regulating the anthocyanin and flavone biosynthesis pathways. Expression of core genes in the phenylpropanoid and anthocyanin pathways was higher in colored than in white petals. Petal color was conferred by flavonoids and anthocyanins, with red and yellow petals rich in anthocyanin and flavonol glycosides, respectively. This study provides new insight on molecular mechanism of recessive epistasis,also has potential breeding value by engineering GaPC to develop colored petals or fibers for multifunctional utilization of cotton.
文摘BACKGROUND A series of long non-coding RNAs(lncRNAs)have been reported to play a crucial role in cancer biology.Some previous studies report that lncRNA CDKN2B-AS1 is involved in some human malignancies.However,its role in hepatocellular carcinoma(HCC)has not been fully deciphered.AIM To decipher the role of CDKN2B-AS1 in the progression of HCC.METHODS CDKN2B-AS1 expression in HCC was detected by quantitative real-time polymerase chain reaction.The malignant phenotypes of Li-7 and SNU-182 cells were detected by the CCK-8 method,EdU method,and flow cytometry,respectively.RNA immunoprecipitation was executed to confirm the interaction between CDKN2B-AS1 and E2F transcription factor 1(E2F1).Luciferase reporter assay and chromatin immunoprecipitation were performed to verify the binding of E2F1 to the promoter of G protein subunit alpha Z(GNAZ).E2F1 and GNAZ were detected by western blot in HCC cells.RESULTS In HCC tissues,CDKN2B-AS1 was upregulated.Depletion of CDKN2B-AS1 inhibited the proliferation of HCC cells,and the depletion of CDKN2B-AS1 also induced cell cycle arrest and apoptosis.CDKN2B-AS1 could interact with E2F1.Depletion of CDKN2B-AS1 inhibited the binding of E2F1 to the GNAZ promoter region.Overexpression of E2F1 reversed the biological effects of depletion of CDKN2B-AS1 on the malignant behaviors of HCC cells.CONCLUSION CDKN2B-AS1 recruits E2F1 to facilitate GNAZ transcription to promote HCC progression.
基金Supported by Sailing Program of Naval Medical University,Program of Shanghai Hongkou District Health Commission,No.2202-27Special Funds for Activating Scientific Research of Shanghai Fourth People’s Hospital,No.sykyqd05801.
文摘BACKGROUND The hypoxic environment during bone healing is important in regulating the differentiation of periosteal stem cells(PSCs)into osteoblasts or chondrocytes;however,the underlying mechanisms remain unclear.AIM To determine the effect of hypoxia on PSCs,and the expression of microRNA-584-5p(miR-584-5p)and RUNX family transcription factor 2(RUNX2)in PSCs was modulated to explore the impact of the miR-584-5p/RUNX2 axis on hypoxiainduced osteogenic differentiation of PSCs.METHODS In this study,we isolated primary mouse PSCs and stimulated them with hypoxia,and the characteristics and functional genes related to PSC osteogenic differentiation were assessed.Constructs expressing miR-584-5p and RUNX2 were established to determine PSC osteogenic differentiation.RESULTS Hypoxic stimulation induced PSC osteogenic differentiation and significantly increased calcified nodules,intracellular calcium ion levels,and alkaline phosphatase(ALP)activity in PSCs.Osteogenic differentiation-related factors such as RUNX2,bone morphogenetic protein 2,hypoxia-inducible factor 1-alpha,and ALP were upregulated;in contrast,miR-584-5p was downregulated in these cells.Furthermore,upregulation of miR-584-5p significantly inhibited RUNX2 expression and hypoxia-induced PSC osteogenic differentiation.RUNX2 was the target gene of miR-584-5p,antagonizing miR-584-5p inhibition in hypoxia-induced PSC osteogenic differentiation.CONCLUSION Our study showed that the interaction of miR-584-5p and RUNX2 could mediate PSC osteogenic differentiation induced by hypoxia.
文摘Objective:To study the correlation of Runt-related transcription factor gene 3 (RUNX3) expression in osteosarcoma tissue with cell proliferation and angiogenesis.Methods: A total of 80 patients with osteosarcoma who were treated in our hospital between February 2014 and February 2017 were collected, and the RUNX3 expression in osteosarcoma tissue and adjacent tissue were detected. According to the RUNX3 expression in tumor tissue, the patients were further divided into high RUNX3 expression group and low RUNX3 expression group, and the proliferation gene and angiogenesis gene expression were compared.Results:RUNX3, KISS-1 and RanBP9 mRNA expression in osteosarcoma tissue were significantly lower than those in adjacent tissue while VCP, Six1, S100A6, IF-1α, MMP-14, bFGF and Ang-2 mRNA expression were significantly higher than those in adjacent tissue;KISS-1 and RanBP9 mRNA expression in osteosarcoma tissue of high RUNX3 expression group were significantly higher than those of low RUNX3 expression group while VCP, Six1, S100A6, IF-1 , MMP-14, bFGF and Ang-2 mRNA expression were significantly lower than those of low RUNX3 expression group.Conclusions:The desease of RUNX3 expression in osteosarcoma tissue is one of the direct causes of increased tumor proliferation activity and strong angiogenesis.
基金the National Natural Science Foundation of China, No. 30872778/C1704the Natural Science Foundation of Beijing, No. 7072023+1 种基金the Clinical Basic Cooperation Foundation of Capital Medical University, No. 2009jl18the Clinical Basic Cooperation Foundation of Capital Medical University, No.11JL-L03
文摘To examine the expression profiles of oligodendrocyte transcription factors 1 and 2 （Oligl and Olig2） and the interaction between these two proteins, Oligl was transfected into the lateral ventricles of neonatal rats subjected to hypoxia. Immunohistochemistry demonstrated that Olig2 was expressed throughout the nuclei in the brain, and expression increased at 3 days following hypoxia and was higher than levels at 7 days following Ad5-Oligl transfection. Western blot revealed that Oligl and Olig2 expression increased in Oligl-transfected brain cells 3 days after hypoxia, but Oligl and Olig2 expression decreased at 7 days. These results indicate that Oligl overexpression enhances Olig2 expression in brain tissues of hypoxia rats.
文摘Among APETALA2 (AP2)-type plant specific transcription factor family, WRINKLED1 (WRI1), has appeared to be a master gene transcriptionally regulating a set of carbon metabolism- and fatty acid synthesis (FAS)-related genes responsible for seed specific triacylglycerols (TAGs) storage in oil plants. B3 type transcription factors, such as ABI3 and FUS3, are known to be involved in seed development, such as seed storage protein synthesis and maturation. Based on the recent whole genome sequence data of castor bean (Ricinus communis L.), putative WRI1 homologs (RcWRI1, RcWRI2) specifically expressed in castor bean seed have been identified by comparing organ specific expression profiles among seed development-related transcription factors, seed storage specific genes (Ricin, RcOleosin) and a set of FAS genes including genes for sucrose synthase (RcSUS2), biotin carboxyl carrier protein (a subunit of acetyl-CoA carboxylase, RcBCCP2) and ketoacyl-acyl carrier protein synthase (RcKAS1). Immunoreactive signals with WRI1, FUS3 and ABI5-related polypeptides were also detected in seed specifically, consistent with the expression profiles of seed development-related genes. The WRI1 binding consensus sites, [CnTnG](n)(7)[CG], designated as the AW-box, were found at the promoter region of RcBCCP2 and RcKAS1. Thus, RcWRI1 possibly play a pivotal role in seed specific TAGs storage during seed development by directly activating FAS -related genes.
基金supported by the National Natural Science Foundation of China(Grant No.31601593)the Young Elite Scientist Sponsorship of China Association for Science and Technology(Grant No.YESS20170108)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20160588).
文摘Transcription factors(TFs)orchestrate the regulation of cellular gene expression and thereby determine cell functionality.In this study,we analyzed the distribution of TFs containing domains,which named as ZnFTFs,both in ascomycete and basidiomycete fungi.We found that ZnFTFs were widely distributed in these fungal species,but there was more expansion of the ZnFTF class in Ascomycota than Basidiomycota.We identified 40 ZnFTFs in Ustilaginoidea virens,and demonstrated the involvement of UvZnFTF1 in vegetative growth,conidiation,pigment biosynthesis and pathogenicity.RNA-Seq analysis suggested that UvZnFTF1 may regulate different nutrient metabolism pathways,the production of secondary metabolites,and the expression of pathogen-host interaction genes and secreted protein-encodi ng genes.Analysis of the distributi on of differe nt fungal TFs in U.virens further dem on strated that UvZnFTFs make up a large TF family and may play essential biological roles in U.virens.
文摘BACKGROUND MicroRNA 34c(miR-34c)has been reported to be associated with malignant types of cancer,however,it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer(GC).AIM To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.METHODS Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients.miR-34c and E2F1 were detected by real-time quantitative PCR(qPCR)and Western blot.In addition,the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods,and changes in miR-34c and E2F1 during this process were measured.Furthermore,E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells.MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin,qPCR was adopted to detect the expression of miR-34c,Western blot was applied to detect the expression levels of E2F1,drug resistance-related proteins and apoptosis-related proteins,and flow cytometry was used for the determination of cell apoptosis and cell cycle status.RESULTS E2F1 was overexpressed while miR-34c was underexpressed in GC.After inducing GC cells to be resistant to paclitaxel and cisplatin,E2F1 expression increased while miR-34c expression decreased.Both silencing E2F1 and overexpressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin,promote cell apoptosis and inhibit cell proliferation.Among which,silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins,while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1,MRP and other drug resistance-related proteins.Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells,and Si E2F1 to paclitaxel combined with cisplatin.CONCLUSION E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin,and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.
基金Supported by (in part) Novartis Pharma GmbH,Germany,BU Transplantation and Immunology (to Lehner F)the Lower Saxony Ministry of Culture and Sciences and the Volk-swagen foundation,Germany,Grant No.25A.5-7251-99-3/00
文摘AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6) and other liverenriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium. METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (recto)sigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays. RESULTS: The gene expression patterning of liverenriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05) whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05). Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4α were most abundantly expressed in the jejunum (P < 0.05). Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3) was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4α and of NGN3 was conf irmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels. CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.
基金supported by the National Natural Science Foundation of China,Nos. 31730031 and 32130060the National Major Project of Research and Development,No. 2017YFA0104700the Natural Science Foundation of Jiangsu Province,No. BK20202013 (all to XSG)。
文摘The key regulators and regeneration-associated genes involved in axonal regeneration of neurons after injury have not been clarified.In high-throughput sequencing,various factors influence the final sequencing results,including the number and size of cells,the depth of sequencing,and the method of cell separation.There is still a lack of research on the detailed molecular expression profile during the regeneration of dorsal root ganglion neuron axon.In this study,we performed lase r-capture microdissection coupled with RNA sequencing on dorsal root ganglion neurons at 0,3,6,and 12 hours and 1,3,and 7 days after sciatic nerve crush in rats.We identified three stages after dorsal root ganglion injury:early(3-12 hours),pre-regeneration(1 day),and regeneration(3-7 days).Gene expression patterns and related function enrichment res ults showed that one module of genes was highly related to axonal regeneration.We verified the up-regulation of activating transcription factor 3(Atf3),Kruppel like factor 6(Klf6),AT-rich inte raction domain 5A(Arid5α),CAMP responsive element modulator(Crem),and FOS like 1,AP-1 transcription factor Subunit(Fosl1) in dorsal root ganglion neurons after injury.Suppressing these transcription factors(Crem,Arid5o,Fosl1 and Klf6) reduced axonal regrowth in vitro.As the hub transcription factor,Atf3 showed higher expression and activity at the preregeneration and regeneration stages.G protein-coupled estrogen receptor 1(Gper1),inte rleukin 12a(Il12α),estrogen receptor 1(ESR1),and interleukin 6(IL6) may be upstream factors that trigger the activation of Atf3 during the repair of axon injury in the early stage.Our study presents the detailed molecular expression profile during axonal regeneration of dorsal root ganglion neurons after peripheral nerve injury.These findings may provide reference for the clinical screening of molecular targets for the treatment of peripheral nerve injury.
基金supported by the Charles H.“Skip”Smith Endowment Fund and the Verne M.Willaman Endowment Fund from the Pennsylvania State University to G.C。
文摘Objective:Glioblastoma(GBM)is the most prevalent and aggressive adult primary cancer in the central nervous system.Therapeutic approaches for GBM treatment are under intense investigation,including the use of emerging immunotherapies.Here,we propose an alternative approach to treat GBM through reprogramming proliferative GBM cells into non-proliferative neurons.Methods:Retroviruses were used to target highly proliferative human GBM cells through overexpression of neural transcription factors.Immunostaining,electrophysiological recording,and bulk RNA-seq were performed to investigate the mechanisms underlying the neuronal conversion of human GBM cells.An in vivo intracranial xenograft mouse model was used to examine the neuronal conversion of human GBM cells.Results:We report efficient neuronal conversion from human GBM cells by overexpressing single neural transcription factor Neurogenic differentiation 1(Neuro D1),Neurogenin-2(Neurog2),or Achaete-scute homolog 1(Ascl1).Subtype characterization showed that the majority of Neurog2-and Neuro D1-converted neurons were glutamatergic,while Ascl1 favored GABAergic neuron generation.The GBM cell-converted neurons not only showed pan-neuronal markers but also exhibited neuron-specific electrophysiological activities.Transcriptome analyses revealed that neuronal genes were activated in glioma cells after overexpression of neural transcription factors,and different signaling pathways were activated by different neural transcription factors.Importantly,the neuronal conversion of GBM cells was accompanied by significant inhibition of GBM cell proliferation in both in vitro and in vivo models.Conclusions:These results suggest that GBM cells can be reprogrammed into different subtypes of neurons,leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.
基金the Natural Science Foundation of Liaoning Province,No.2023-MS-149.
文摘BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1(VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer(CRC). Knockdown of VASH1 enhanced transforming growth factor-β1(TGF-β1)/Smad3 pathway activity and type Ⅰ/Ⅲ collagen production. Our previous findings suggest that ELL-associated factor 2(EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3(STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was upregulated in advanced CRC tissue compared to normal colorectal tissue. KaplanMeier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cellderived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.
