Upregulation of MicroRNA-935 Promotes the Malignant Behaviors of Pancreatic Carcinoma PANC-1 Cells via Targeting Inositol Polyphosphate 4-Phosphatase Type I Gene (INPP4A).

Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated, while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with the miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells. Moreover, suppression of miR-935 resulted in a significant increase in the expression of p27. Also, suppression of miR-935 resulted in significant expression changes of EMT markers; E-cadherin was significantly upregulated, while N-cadherin, Snail, and vimentin were markedly downregulated. In addition, after suppression of miR-935, the expression of apoptosis-related proteins was also changed; Bax was significantly upregulated while Bcl-2, procaspase 3, and active caspase 3 were obviously downregulated. Importantly, opposite effects were obtained when miR-935 was overexpressed by transfection with the miR-935 mimic. In addition, INPP4A was a direct target of miR-935. Silencing of INPP4A significantly counteracted the effects of miR-935 suppression on cell migration and apoptosis, as well as the expression changes of the above EMT- and apoptosis-related molecules. Our findings indicate that upregulation of miR-935 may promote pancreatic cancer cell proliferation and migration and inhibit cell apoptosis by targeting INPP4A. miR-935 and INPP4A may serve as potential targets in the therapy of pancreatic cancer.