miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer

Mol Ther Nucleic Acids. 2018 Dec 7:13:121-132. doi: 10.1016/j.omtn.2018.08.012. Epub 2018 Aug 22.

Abstract

Extensive research has suggested that miR-7 plays a critical role in cancer progression. However, the biological function of miR-7 in pancreatic cancer (PC) progression is poorly understood. Therefore, in the present study, we investigated the function of miR-7 and its molecular mechanism in PC progression. We used multiple methods, such as MTT, FACS, Transwell assay, RT-PCR, western blotting, and transfection to investigate the role of miR-7 in PC cells. We found that miR-7 suppressed cell growth, migration, and invasion but induced apoptosis in PC cells. Moreover, overexpression of miR-7 repressed tumor growth in mice, suggesting that miR-7 could exert its tumor-suppressive function in PC. Mechanistically, we validated that MAP3K9 is a direct target of miR-7, which significantly enhanced PC cell proliferation and inhibited cell apoptosis partly through activation of the MEK/ERK pathway and NF-κB pathway. Moreover, rescue experiments also showed that miR-7 suppressed PC cell proliferation and induced PC cell apoptosis by directly targeting MAP3K9, leading to inhibition of the MEK/ERK and NF-κB pathways. Taken together, these results suggest that miR-7/MAP3K9 is critically involved in PC progression and that miR-7 may be a potential target for PC treatment.

Keywords: MAP3K9; cell growth; invasion; miR-7; pancreatic cancer.