miR-145 suppresses the proliferation, invasion and migration of NSCLC cells by regulating the BAX/BCL-2 ratio and the caspase-3 cascade

Oncol Lett. 2018 Apr;15(4):4337-4343. doi: 10.3892/ol.2018.7863. Epub 2018 Jan 25.

Abstract

Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. In vitro cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis. The results demonstrated that ectopic expression of miR-145 inhibited the proliferation, invasion and migration of A549 cells, but promoted the apoptosis of A549 cells. Western blot analysis indicated that increased miR-145 levels led to a marked decrease in the expression of MMP-2, MMP-9 and Bcl-2. Upregulation of miR-145 expression increased the expression of Bax, thus increasing the Bax/Bcl-2 ratio. Additionally, the results indicated that miR-145 over expression promoted the cleavage of caspase-3 and PARP. Taken together, these results indicated that miR-145 suppresses the proliferative, invasive and migratory ability of A549 cells. Additionally, miR-145 upregulation induced apoptosis of A549 cells possibly by decreasing MMP-2 and MMP-9 expression, the Bax/Bcl-2 ratio and the activity of the caspase-3 cascade.

Keywords: B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 ratio; invasion; migration; non-small cell lung cancer; proliferation.