The tumor suppressor role and ceRNA network of miR-1294 in cancer

miRNAs are endogenous small RNAs that are important regulators of gene expression.miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators.miR-1294 affects the proliferation,migration,invasion,and apoptosis of cancer cells.The target genes of miR-1294 are involved in the PI3K/AKT/mTOR,RAS,and JAK/STAT signaling pathways.Six target genes of miR-1294 are the targets of a variety of drugs.Low expression of miR-1294 is associated with resistance to cisplatin and TMZ and a poorer prognosis in patients with ESCC,GC,EOC,PDAC,or NSCLC.Therefore,this work outlines the molecular mechanisms and provides a basis for the clinical significance of the tumor suppressor miR-1294 in cancer.

PRKCDBP Methylation is a Potential and Promising Candidate Biomarker for Non-small Cell Lung Cancer

Background and objectives:The occurrence and development of lung cancer are closely linked to epigenetic modification.Abnormal DNA methylation in the CpG island region of genes has been found in many cancers.Protein kinase C delta binding protein(PRKCDBP) is a potential tumor suppressor and its epigenetic changes are found in many human malignancies.This study investigated the possibility of PRKCDBP methylation as a potential biomarker for non-small cell lung cancer(NSCLC).Methods:We measured the methylation levels of PRKCDBP in the three groups of NSCLC tissues.Promoter activity was measured by the dual luciferase assay,with S’-aza-deoxycytidine to examine the effect of demethylation on the expression level of PRKCDBP.Results:The methylation levels of PRKCDBP in tumor tissues and 3 cm para-tumor were higher than those of distant(>10 cm)non-tumor tissues.Receiver operating characteristic(ROC) curve analysis between tumor tissues and distant non-tumor tissues showed that the area under the line(AUC) was 0.717.Dual luciferase experiment confirmed that the promoter region was able to promote gene expression.Meanwhile,in vitro methylation of the fragment(PRKCDBP;e) could significantly reduce the promoter activity of the fragment.Demethylation of 5’-aza-deoxycytidine in lung cancer cell lines A549 and H1299 showed a significant up-regulation of PRKCDBP mRNA levels.Conclusion:PRKCDBP methylation is a potential and promising candidate biomarker for non-small cell lung cancer.

Association of four GSTs gene polymorphisms with Parkinson disease: A meta-analysis

Parkinson disease (PD) is a neurological disorder with huge destruction to human body, which affects approximately 2% of the population aged 65 years or older. As antioxidants in the stress defence systems, glutathione S-transferases (GSTs) are dimeric cytosolic enzymes with an important role in the pathogenesis of PD. The aim of this study was to evaluate the association between the polymorphisms of GST genes and PD. Meta-analyses were conducted from 17 studies (38 stages) among 3419 cases and 5686 controls between four polymorphisms (GSTT1 deletion polymorphism;GSTM1 deletion polymorphism;GSTP1-104: rs1695;GSTP1-114: rs1799811) and PD. There is no significant association between the four GST gene variants and PD. A further subgroup study by ethnicity observed a risky role of GSTM1 deletion polymorphism with PD in Europeans (p = 0.013, OR = 1.126, 95% CI = 1.025-1.236), and a protective role of GSTM1 deletion polymorphism with PD in Latin Americans (p = 0.032, OR = 0.750, 95% CI = 0.577-0.975). Our meta-analysis suggested that GSTM1 deletion polymorphism increased the risk of PD in Europeans, but reduced the risk of PD in Latin Americans. Future large-scale studies might be needed to confirm the ethnic difference of GSTM1 deletion polymorphism, and to check whether there was significant association of PD for other GST genetic polymorphisms.

A comprehensive meta-analysis of the association between three <i>IL</i>1B polymorphisms and rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated chronic inflammatory disease that causes huge destruction to human body. IL1B encodes key mediator IL-1β protein, which plays an important role in the pathogenesis of inflammatory syndromes. The aim of this study was to evaluate the association between IL1B polymorphisms and RA. A meta-analysis was performed on the association between three IL1B polymorphisms (IL1B-31: rs1143627;IL1B-511: rs16944;IL1B + 3954: rs1143634) and RA. A trend of significant association was observed between IL1B + 3954 and RA (p = 0.06, odd ratio (OR) = 1.19, 95% confidential interval (CI) = 1.00-1.42). A significant association was found in Europeans under the dominant model between IL1B-511T and RA (p = 0.03, OR = 0.89, 95% CI = 0.81-0.99). Our meta-analysis indicated that IL1B ? 511-T played a protective role against RA in Europeans, and that IL1B + 3954-T had the potential to increase the risk of RA. Future large-scale studies should be considered to confirm the association between IL1B polymorphisms and RA.

Meta-analyses of nine polymorphisms of six genes with the risk of schizophrenia

The aim of this study was to determine whether 9 genetic polymorphisms confered susceptibility to schizophrenia (SCZ). The authors conducted meta-analyses on associations between SCZ and 9 variants of 6 genes including PIK3C3 (432C > T), ABCB1 (C3435T and G2677T), CTLA4 (+49A/G), OLIG2 (rs762178), GAD1 (rs1978340, rs3749034 and rs769395), and GRIN1 (G1001C). A total of 34 case-control studies were involved in our meta-analyses. Our results showed no significant association between all the loci and SCZ. This meta-analysis confirmed a lack of association of SCZ for 9 genetic polymorphisms including GRIN1 G1001C, ABCB1 C3435T and G2677T, CTLA4 + 49A/G, OLIG2 rs762178, GAD1 gene rs1978340, rs3749034 and rs769395, and PIK3C3 432C > T.

Current insights into the oncogenic roles of lncRNA LINC00355

Long noncoding RNAs(lncRNAs)are a class of nonprotein-coding transcripts that are longer than 200 nucleotides.LINC00355 is a lncRNA located on chromosome 13q21.31 and is consistently upregulated in various cancers.It regulates the expression of downstream genes at both transcriptional and posttranscriptional levels,including eight microRNAs(miR-15a-5p,miR-34b-5p,miR-424-5p,miR-1225,miR-217-5p,miR-6777-3p,miR-195,and miR-466)and three protein-coding genes(ITGA2,RAD18,and UBE3C).LINC00355 plays a role in regulating various biological processes such as cell cycle progression,proliferation,apoptosis,epithelial-mesenchymal transition,invasion,and metastasis of cancer cells.It is involved in the regulation of the Wnt/β-catenin signaling pathway and p53 signaling pathway.Upregulation of LINC00355 has been identified as a high-risk factor in cancer patients and its increased expression is associated with poorer overall survival,recurrence-free survival,and disease-free survival.LINC00355 upregulation has been linked to several unfavorable clinical characteristics,including advanced tumor node metastasis and World Health Organization stages,reduced Karnofsky Performance Scale scores,increased tumor size,greater depth of invasion,and more extensive lymph node metastasis.LINC00355 induces chemotherapy resistance in cancer cells by regulating five downstream genes,namely HMGA2,ABCB1,ITGA2,WNT10B,and CCNE1 genes.In summary,LINC00355 is a potential oncogene with great potential as a diagnostic marker and therapeutic target for cancer.

Complete genome sequence of high-yield strain S. lincolnensis B48 and identification of crucial mutations contributing to lincomycin overproduction

The lincosamide family antibiotic lincomycin is a widely used antibacterial pharmaceutical generated by Streptomyces lincolnensis,and the high-yield strain B48 produces 2.5 g/L lincomycin,approximately 30-fold as the wild-type strain NRRL 2936.Here,the genome of S.lincolnensis B48 was completely sequenced,revealing a^10.0 Mb single chromosome with 71.03%G+C content.Based on the genomic information,lincomycinrelated primary metabolism network was constructed and the secondary metabolic potential was analyzed.In order to dissect the overproduction mechanism,a comparative genomic analysis with NRRL 2936 was performed.Three large deletions(LDI-III),one large inverted duplication(LID),one long inversion and 80 small variations(including 50 single nucleotide variations,13 insertions and 17 deletions)were found in B48 genome.Then several crucial mutants contributing to higher production phenotype were validated.Deleting of a MarRtype regulator-encoding gene slinc377 from LDI,and the whole 24.7 kb LDII in NRRL 2936 enhanced lincomycin titer by 244%and 284%,respectively.Besides,lincomycin production of NRRL 2936 was increased to 7.7-fold when a 71 kb supercluster BGC33 from LDIII was eliminated.As for the duplication region,overexpression of the cluster situated genes lmbB2 and lmbU,as well as two novel transcriptional regulator-encoding genes(slinc191 and slinc348)elevated lincomycin titer by 77%,75%,114%and 702%,respectively.Furthermore,three negative correlation genes(slinc6156,slinc4481 and slinc6011)on lincomycin biosynthesis,participating in regulation were found out.And surprisingly,inactivation of RNase J-encoding gene slinc6156 and TPR(tetratricopeptide repeat)domain-containing protein-encoding gene slinc4481 achieved lincomycin titer equivalent to 83%and 68%of B48,respectively,to 22.4 and 18.4-fold compared to NRRL 2936.Therefore,the comparative genomics approach combined with confirmatory experiments identified that large fragment deletion,long sequence duplication,along with several mutations of genes,especially regulator genes,are crucial for lincomycin overproduction.

The paradoxical roles of miR-4295 in human cancer:Implications in pathogenesis and personalized medicine

MiR-4295,located on chromosome 10q25.2,is a unique miRNA with a wide range of biological functions.miR-4295 is widely expressed in vivo,participating in the biological processes of multiple cancers.Although miR-4295 is dysregulated in various cancers,it has also been found to have the function of inhibiting cancer.At the same time,the expression of miR-4295 is related to prognosis and can be affected by numerous factors connecting to the therapeutic effects of various drugs.This article is to better summarize the role of miR-4295 in cancer and review the potential diagnostic,prognostic,and therapeutic value of miR-4295,which may provide insight into subsequent research.

Current and future perspectives on the regulation and functions of miR-545 in cancer development

Micro ribonucleic acids(miRNAs)are a highly conserved class of single-stranded non-coding RNAs.Within the miR-545/374a cluster,miR-545 resides in the intron of the long non-coding RNA(lncRNA)FTX on Xq13.2.The precursor form,pre-miR-545,is cleaved to generate two mature miRNAs,miR-545-3p and miR-545-5p.Remarkably,these two miRNAs exhibit distinct aberrant expression patterns in different cancers;however,their expression in colorectal cancer remains controversial.Notably,miR-545-3p is affected by 15 circular RNAs(circRNAs)and 10 long non-coding RNAs(lncRNAs),and it targets 27 protein-coding genes(PCGs)that participate in the regulation of four signaling pathways.In contrast,miR-545-5p is regulated by one circRNA and five lncRNAs,it targets six PCGs and contributes to the regulation of one signaling pathway.Both miR-545-3p and miR-545-5p affect crucial cellular behaviors,including cell cycle,proliferation,apoptosis,epithelial-mesenchymal transition,invasion,and migration.Although low miR-545-3p expression is associated with poor prognosis in three cancer types,studies on miR-545-5p are yet to be reported.miR-545-3p operates within a diverse range of regulatory networks,thereby augmenting the efficacy of cancer chemotherapy,radiotherapy,and immunotherapy.Conversely,miR-545-5p enhances immunotherapy efficacy by inhibiting T-cell immunoglobulin and mucin-domain containing-3(TIM-3)expression.In summary,miR-545 holds immense potential as a cancer biomarker and therapeutic target.The aberrant expression and regulatory mechanisms of miR-545 in cancer warrant further investigation.