Gastric cancer is one of the most lethal malignancies worldwide. The aberrant expression of microRNA-31 (miR-31) has been reported in gastric cancer; however, its regulation mechanisms are still unclear. Here, we confirmed that miR-31 expression was significantly decreased in gastric cancer tissue and cell lines. Ectopic expression of miR-31 potentially suppresses proliferation and induced early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was associated with promoter DNA methylation status in gastric cancer and cell lines. Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3′-UTR from the results of luciferase reporter assays, qRT-PCR, and western blotting. HDAC2 played an activation role in tumor growth, whose expression is upregulated and inversely associated with miR-31 levels. All the results suggested that miR-31 function as a crucial tumor suppressor was regulated by epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA methylation-miRNA expression-target gene-tumor progression in gastric cancer, and also provided implications for molecular diagnosis and therapeutics of gastric malignancies by detecting miR-31 as a potential target
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