MicroRNA-1285 inhibits malignant biological behaviors of human pancreatic cancer cells by negative regulation of YAP1

Pancreatic ductal adenocarcinoma is a most deadly malignancy, with a 5-year survival rate of similar to 7%. Chemotherapy is the main treatment strategy of this disease. However, the high rate of resistance to chemotherapeutic agent contributes to poor prognosis. MicroRNAs are essential for the initiation, progression and chemoresistance of human malignancies. Previous studies have shown that miRNA-1285 participates in renal cell carcinoma and hepatocellular carcinoma. However, its roles in pancreatic ductal adenocarcinoma are poorly understood. In this study, we confirmed that miR-1285 was significantly down-regulated in gemcitabine-resistant pancreatic cancer cell lines by qRT-PCR. We found that miR-1285 suppressed cell proliferation as well as increased the sensitivity of PDAC cells to gemcitabine by CCK8 assays in vitro. Results from transwell assay indicated that miR-1285 inhibited pancreatic cancer cell migration and invasion. Experiments using different cell lines got identical results. All those results demonstrated that miR-1285 act as tumor suppressor of pancreatic cancer. To our knowledge, this study is the first to elucidate the function of miR-1285 in pancreatic cancer. Western blotting analysis verified that miR-1285 negatively regulated YAP1 protein level, together with EGFR and beta-catenin. YAP1 is a known oncoprotein of pancreatic cancer. As silencing of YAP1 activity might be beneficial in cancer prevention and treatment, our results suggest that miR-1285 might serve as a novel therapeutic target for miRNA-based therapy in pancreatic cancer. Further research elucidating the exact mechanisms of miRNA-1285 function and the correlation between miR-1285 levels in tissues or serum and clinical characteristics of pancreatic cancer is needed later.