MicroRNA-136 inhibits colon cancer cell proliferation and invasion through targeting liver receptor homolog-1/Wnt signaling

Abstract

An increasing number of studies have reported that microRNAs (miRNAs) are involved in the malignant behavior of colon cancer cells through directly targeting multiple tumor suppressors or oncogenes. The expression and role of miR-136 has been reported in several types of human cancer. However, the role of miR-136 in colon cancer remains unclear. In this study, we aimed to investigate the expression and function of miR-136 in colon cancer and the potential underlying mechanism. Here, we found that miR-136 was decreased in colon cancer cell lines and tissues. Overexpression of miR-136 inhibited the proliferation and invasion in SW480 and HCT116 cell lines while suppression of miR-136 exhibited the opposite effect. Liver receptor homolog-1 (LRH-1) was identified as a direct target gene of miR-136. Notably, miR-136 overexpression suppressed LRH-1 expression as well as Wnt signaling in SW480 and HCT116 cell lines. The miR-136 expression level inversely correlated with LRH-1 mRNA expression in colon cancer specimens. Moreover, overexpression of LRH-1 partially reversed the miR-136-induced antitumor effect in SW480 and HCT116 cell lines. Taken together, these findings suggest that miR-136 functions as a negative regulator in colon cancer progression by targeting LRH-1 and that miR-136 downregulation contributes to high expression of LRH-1 and aberrant activation of Wnt signaling, leaving open the possibility that miR-136 may serve as a potential therapeutic target for colon cancer.