The association between rs2476601 polymorphism in PTPN22 gene and risk of alopecia areata: A meta-analysis of case-control studies.

BACKGROUND: The single nucleotide polymorphism (SNP) rs2476601 of the protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) gene has been presented to implicate in the pathogenesis of alopecia areata (AA) in a few association investigations with limited sample size and inconsistent conclusions. METHODS: The aim of the current meta-analysis was to assess and synthesize the presently available data on the connection between rs2476601 and AA vulnerability. Six electronic databases, including EMBASE, PubMed, Web of Science, the Cochrane Library, Wanfang data, and the China National Knowledge Infrastructure database (CNKI), were systematically retrieved for relevant observational studies published previous to November 2018. Total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the correlation between PTPN22 polymorphism and AA. Risk of bias was estimated according to the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were carried out using the RevMan 5.3 software. RESULTS: In general, 5 case-control studies including 1129 AA patients and 1702 healthy control individuals were obtained for this meta-analysis. The pooled results suggested that rs2476601 SNP was significantly associated with AA susceptibility under allelic model (C vs T, OR = 0.77, 95% CI, 0.64-0.92, P = .003) and recessive model (CC vs CT + TT, OR = 0.73, 95% CI, 0.60-0.88, P = .001). CONCLUSION: On the basis of the results of the current research, the rs2476601 polymorphism of PTPN22 gene is significantly correlated with AA susceptibility. The C-allele and CC-genotype carriers at this locus have a lower risk of AA.

MiR-497-5p, miR-195-5p and miR-455-3p function as tumor suppressors by targeting hTERT in melanoma A375 cells.

BACKGROUND: hTERT gene plays an important role in melanoma, although the specific mechanism involved is unclear. The aim of this study was to screen and identify the relative miRNAs with the regulation of hTERT in melanoma. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to detect hTERT mRNA and protein expression in 36 formalin-fixed paraffin-embedded melanoma tissues and 36 age- and sex-matched pigmented nevi cases, respectively. Bioinformatics analysis and custom miRNA polymerase chain reaction array were determined for predicting, screening and verifying miRNAs with the regulation of the hTERT gene. To investigate the biological functions, miRNAs mimics or inhibitors were transfected into melanoma A375 cells. The relative expression of miR-497-5p, miR-195-5p, miR-455-3p and hTERT mRNA was determined by q-PCR. The protein expression of hTERT was detected by Western blot. 3-(4,5-Dimethylthiazolyl-2-yl)-2,5-biphenyl tetrazolium bromide and flow cytometry were employed to detect cell proliferation ability, cell apoptosis and cell cycle. Transwell and wound healing assays were used to observe cell invasion and migration abilities. A direct target gene of miRNAs was analyzed by a dual luciferase reporter activity assay. RESULTS: MiR-497-5p, miR-195-5p, miR-455-3p were significantly downregulated, while hTERT was upregulated in melanoma tissues. hTERT expression level was inversely correlated with miR-497-5p, miR-195-5p and miR-455-3p. Overexpression of miR-497-5p, miR-195-5p and miR-455-3p inhibited A375 cell proliferation, migration and invasion, arrested the cell cycle, induced cell apoptosis and decreased hTERT expression at both mRNA and protein levels. Suppression of miR-497-5p, miR-195-5p and miR-455-3p partially reversed the inhibitory effects. Finally, hTERT was identified as a direct target of miR-497-5p, miR-195-5p and miR-455-3p. CONCLUSIONS: MiR-497-5p, miR-195-5p and miR-455-3p act as tumor suppressors by targeting hTERT in melanoma A375 cells. Therefore, miR-497-5p, miR-195-5p and miR-455-3p could be potential targeted therapeutic choice for melanoma.