MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met

Am J Transl Res. 2017 May 15;9(5):2437-2446. eCollection 2017.

Abstract

MicroRNA-144-3p (miR-144-3p) has been implicated in the development of many types of cancer. However, its role in multiple myeloma (MM) remains largely unknown. In this study, we found that miR-144-3p was downregulated in both MM cell lines and plasma from patients with MM. In vitro studies further showed that transfection of an miR-144-3p mimic into MM cells inhibited their proliferation and colony formation, and promoted cell cycle arrest at the G0/G1 phase and apoptosis. In addition, we found that miR-144-3p could directly target the 3'-untranslated region of cellular-mesenchymal to epithelial transition factor (c-MET) and suppress c-MET expression and its downstream signaling pathway (PI3K/AKT). Rescue experiments revealed that overexpression of c-MET partially reversed the inhibition effect of miR-144-3p in MM cells. In vivo studies confirmed that restoration of miR-144-3p suppressed tumor growth in xenograft nude mice by repressing c-MET. Overall, these findings demonstrate that miR-144-3p functions as a tumor suppressor in MM by targeting c-MET, suggesting that miR-144-3p might serve as a potential therapeutic target in MM.

Keywords: MiR-144-3p; apoptosis; c-MET; multiple myeloma; proliferation.