Overexpression of microRNA-495 improves the intestinal mucosal barrier function by targeting STAT3 via inhibition of the JAK/STAT3 signaling pathway in a mouse model of ulcerative colitis.

We aim to investigate the role of microRNA-495 (miR-495) in the intestinal mucosal barrier by indirectly targeting signal transducer and activator of transcription 3 (STAT3) through the Janus kinase-signal transducer and activator of transcription (JAK)/STAT3 signaling pathway in a mouse model of ulcerative colitis (UC). BALB/c mice were selected for establishing mice model of UC, and intestinal tissues of normal and UC mice were collected. ELISA was conducted for detecting levels of TNF-α, IL-6, IFN-γ and IL-10. The levels of SOD, MPO, MDA and NO were tested in the intestinal tissues. Dual luciferase reporter gene assay was applied to determine whether miR-495 directly targets STAT3. Cells were cultured, transfected and assigned into: normal group, blank group, NC group, miR-495 mimic group, miR-495 inhibitor group, siRNA-STAT3 group and miR-495 inhibitor+siRNA-STAT3 group. MTT was used for testing cell proliferation, flow cytometry for cell cycle and apoptosis. Northern blotting and Western blotting were performed to detect miR-495 expression and expressions of STAT3, JAK and Claudin-1. Results show that the UC group had higher expression levels of TNF-α, IL-6, IFN-γ, MPO, MDA, NO, STAT3 and JAK and lower expression levels of IL-10, SOD, miR-495 and Claudin-1, compared to the normal group. Dual luciferase reporter gene assay confirmed that STAT3 was the target gene of miR-495. The miR-495 mimic and siRNA-STAT3 groups had higher expressions of Claudin-1, higher cell proliferation and increased amount of cells in S phase, but lower expressions of STAT3 and JAK, decreased amount of cells in G0/G1 phase and cell apoptotic rate compared with the blank, NC groups. We also found that the miR-495 inhibitor+siRNA-STAT3 group had reduced miR-495 expression. No significant differences were found in mRNA and protein expressions of STAT3, JAK and Claudin-1, cell proliferation, apoptosis and cycle amongst the miR-495 inhibitor+siRNA-STAT3 groups. Our study provides evidence that miR-495 improves the intestinal mucosal barrier function by targeting STAT3 through inhibiting the JAK/STAT3 signaling pathway in UC mice.

Association between cadherin-17 expression and pathological characteristics of gastric cancer: a meta-analysis.

AIM: To construct a meta-analysis in order to examine the relationship between cadherin-17 (CDH17) and gastric cancer (GC). METHODS: Related articles were selected by searching the following English or Chinese electronic databases: CINAHL, MEDLINE, Science Citation Index, the Chinese Journal Full-Text, and the Weipu Journal. Newcastle-Ottawa Scale (NOS) criteria were used to ensure consistency in reviewing and reporting results. Statistical analyses were conducted with Version 12.0 STATA statistical software. RESULTS: Ultimately, 11 articles, with a total of 2,120 GC patients, were found to be eligible for study inclusion. In comparisons of GC patients by TNM stage (III-IV vs I-II: OR = 2.35, 95%CI: 1.15-4.825, P = 0.019), histologic grade (3-4 vs 1-2: OR = 3.48, 95%CI: 1.36-8.92, P = 0.009), invasion grade (T3-4 vs T1-2: OR = 2.86; 95%CI: 1.69-4.83; P = 0.000), and lymph node metastasis (positive vs negative: OR = 2.64; 95%CI: 1.33-5.27; P = 0.006), it was found that CDH17 showed more positive expressions in each of the more severe cases. Country-stratified analyses from all four experimental subgroups showed that high CDH17 expression levels may be related to GC among Chinese and Korean populations (all P < 0.05), with the exception of the invasion grade T3-4 vs T1-2 comparison, where the relation only held among the Chinese population (OR = 2.86, 95%CI: 1.69-4.83, P = 0.000). CONCLUSION: Collectively, the data reflects the capacity of CDH17 in tumor proliferation and metastasis among GC patients.

Correlations of MMP-2 and TIMP-2 gene polymorphisms with the risk and prognosis of gastric cancer.

AIM: To investigate the correlations of MMP-2 and TIMP-2 polymorphisms with the risk and prognosis of gastric cancer (GC). METHODS: With an incorporation of 254 GC patients in the case group and 250 healthy subjects enrolled as the control group, this experiment was conducted. Denaturing high performance liquid chromatography method was adopted to detect all genotypes under partial denaturation, haloptype analysis was completed with the Shesis software. Serum MMP-2 and TIMP-2 levels were determined by the immunohistochemical semi-quantitative analysis. The follow-up examination was conducted after the patients had completed systemic therapy and discharged. RESULTS: The distribution frequencies of MMP-2-735C/T locus genotypes between groups were compared (P > 0.05). However, the distributions of alleles and genotype frequencies of MMP-2-1306C/T, TIMP-2-303G/A and -418G/C all exhibited statistical difference (all P < 0.05). The gene polymorphism of MMP-2-1306C/T was statistically correlated with the expression of MMP-2 protein (P < 0.05); the same result was also found regarding TIMP-2-303G/A (P < 0.05). The haplotype analysis revealed that the CGC frequency of the case group was apparently higher than that of the control group (P < 0.05), the positive survival rate of CGC was apparently lower than the negative one. CONCLUSION: MMP-2-1306C/T, TIMP-2-303G/A and -418G/C variants might be correlated with GC susceptibility. Serum MMP-2 and TIMP-2 protein levels might be associated with GC susceptibility; Additionally, CGC haplotype might be the risk factor of GC.