Oleanolic acid suppresses the proliferation of lung carcinoma cells by miR-122/Cyclin G1/MEF2D axis

Abstract

Oleanolic acid (OA) is a natural compound from plants with anti-tumor activities. However, the mechanism of the inhibitory effect of OA on cell cycle progression has not been completely explored. We employed several lung carcinoma cell lines to investigate the cell cycle-related molecular pathway affected by OA. The data revealed that OA suppressed the proliferation of lung cancer cells in both dose- and time-dependent manners, along with an increase in miR-122 abundance. The suppression of miR-122 abolished the effect of OA on lung cancer cells. CCNG1 and MEF2D, two putative miR-122 targets, were found to be downregulated by OA treatment. Restoring their expression counteracted the effect of OA on lung carcinoma cells. OA was further shown to induce the expression of miR-122-regulating transcriptional factors in lung cancer cells. Collectively, OA induced cell cycle arrest in lung cancer cells through miR-122/Cyclin G1/MEF2D pathway. This finding may contribute to the understanding of the molecular mechanism of OA's anti-tumor activity.