ABSTRACT
Previous research has revealed that microRNA-361 (miR-361) functions as a fundamental modulator in non-small-cell lung cancer and esophageal carcinoma. However, its involvement in pancreatic cancer (PC) is yet to be elucidated. Therefore, the present study aimed to examine the mechanism and function of miR-361 during the regulation of PC cell migration and viability. It was demonstrated that miR-361 expression decreased in PC cell lines and tissues, and the overexpression of miR-361 suppressed in vivo PC cell proliferation in mice. Moreover, flow cytometry and MTT assays indicated that the miR-361 mimic decreased the viability and increased the apoptosis of PC cells. Both Transwell migration and wound healing assays identified that miR-361 ameliorated the migratory ability of PC cells. Using dual-luciferase reporter assays, it was found that miR-361 targeted mitogen-activated protein kinase (MAPK)/JNK 3'-untranslated regions, inducing the downregulation of this gene. In PC cells, overexpression of MAPK/JNK diminished the pro-apoptotic effect of the miR-361 mimic, while restoring the migratory activity of PC cells. Collectively, the present results suggested novel molecular mechanisms underlying PC progression and development.
ABSTRACT
AIMS: Associations between polymorphisms in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)/mannose-binding lectin (MBL)/interleukin-4 (IL-4)/interleukin-6 (IL-6)/phospholipase C ε-1 (PLCE1) and gastric cancer (GC) were already reported by many studies, yet the conclusions of these studies were somehow controversial. The aim of this meta-analysis was to better clarify associations between polymorphisms in CTLA-4/MBL/IL-4/IL-6/PLCE1 and GC by combing the results of all relevant studies. METHODS: Eligible studies were searched from PubMed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. RESULTS: Forty-three studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs5742909 (dominant comparison: OR: 1.58, 95 % CI: 1.01 to 2.48; allele comparison: OR: 1.69, 95 % CI: 1.12 to 2.56) and PLCE1 rs2274223 (dominant comparison: OR: 0.84, 95 % CI: 0.72 to 0.98; recessive comparison: OR: 1.23, 95 % CI: 1.08 to 1.40; over-dominant comparison: OR: 1.16, 95 % CI: 1.00 to 1.34; allele comparison: OR 0.88, 95 % CI 0.78 to 0.99) polymorphisms were significantly associated with GC in the general population. We also obtained similar significant associations with GC for rs5742909 and rs2274223 polymorphisms in East Asians. Nevertheless, no positive results were observed for the other eight investigated polymorphisms. CONCLUSION: Collectively, this meta-analysis demonstrated that CTLA-4 rs5742909 and PLCE1 rs2274223 polymorphisms may confer susceptibility to GC, especially for East Asians.
