MicroRNA-376c suppresses non-small-cell lung cancer cell growth and invasion by targeting LRH-1-mediated Wnt signaling pathway

Abstract

MicroRNAs (miRNAs) that negatively regulate gene expression have emerged as novel therapeutic tools for cancer treatment. In this study, we investigated the potential role of Liver receptor homolog-1 (LRH-1), a novel oncogene, in non-small-cell lung cancer (NSCLC), and examined the regulation of LRH-1 by miRNAs. We found that LRH-1 was highly overexpressed in NSCLC cell lines. Knockdown of LRH-1 by small interfering RNA significantly inhibited NSCLC cell growth and invasion. miR-376c directly targeted the 3’-untranslated region (UTR) of LRH-1 and negatively regulated LRH-1 expression, as detected by dual-luciferase reporter assay, real-time quantitative polymerase chain reaction and Western blot analysis. Further data showed that miR-376c expression was inversely correlated with LRH-1 expression in clinical cancer samples. Overexpression of miR-376c could inhibit NSCLC cell growth and invasion as well as Wnt signaling. In contrast, depletion of miR-376c exhibited the opposite effects. Moreover, these effects of miR-376c overexpression were partially abrogated by overexpression of LRH-1. Taken together, these results indicate that LRH-1 is involved in regulating the growth and invasion of NSCLC cells and that miR-376c inhibits NSCLC cell growth and invasion by targeting LRH-1, providing a novel insight into the potential for development of anti-cancer drugs for NSCLC.