MicroRNA-374 targets JAM-2 regulates the growth and metastasis of human pancreatic cancer cells.

Pancreatic cancer is one of the devastating human cancers responsible for tremendous human mortality. Current study was undertaken to explore the therapeutic potential of microRNA-374 in human pancreatic cancer. The results showed that microRNA-374 exhibited lower expression in pancreatic cancer cells and tissues. Overexpression of microRNA-374 in cancer cells resulted in significant decrease in the cell viability. The inhibition of the cell viability was mainly due to the induction of apoptosis as evident from the DAPI and AO/EB staining. Annexin V/PI staining also showed that the overexpression of microRNA-374 enhanced the percentage of apoptotic cells. The western blot analysis showed that microRNA-374 overexpression increases Bax and decreased the Bcl-2 expression. The cleaved PARP and Cleaved caspase-3 expression was also considerably increased upon miR-374 overexpression. The TargetScan analysis together with the dual luciferase assay showed that microRNA-374 targets JAM-2 by binding to mRNA at 3'-UTR. The qRT-PCR analysis showed that JAM-2 was significantly upregulated in the pancreatic cancer cell lines and tissues. Moreover, Overexpression of miR-374 suppressed the expression of JAM-2. Additionally, suppression of JAM-2 also inhibited the viability of the pancreatic cancer cells. In vivo studies in xenografted mice models showed that microRNA-374 expression is effective in suppressing the growth and volume of pancreatic tumors. In conclusion, microRNA-374 is downregulated in pancreatic cancers and may exhibit therapeutic implications in the pancreatic cancer treatment. AJTR