Yuan Qinggong, Cao Gang, Li Junhui, Zhang Yan, Yang Wenbin
Department of General Surgery, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710004, China.
Department of General Surgery, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710004, China.
Gene. 2017 Sep 10;628:48-55. doi: 10.1016/j.gene.2017.07.031. Epub 2017 Jul 12.
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.
越来越多的研究报道，微小RNA（miRNA）通过直接靶向多种肿瘤抑制因子或癌基因参与结肠癌细胞的恶性行为。miR-136在几种人类癌症中的表达及作用已有报道。然而，miR-136在结肠癌中的作用仍不清楚。在本研究中，我们旨在探讨miR-136在结肠癌中的表达、功能及其潜在的机制。在此，我们发现miR-136在结肠癌细胞系和组织中表达降低。miR-136过表达抑制了SW480和HCT116细胞系的增殖和侵袭，而抑制miR-136则表现出相反的效果。肝受体同源物-1（LRH-1）被鉴定为miR-136的直接靶基因。值得注意的是，miR-136过表达抑制了SW480和HCT116细胞系中LRH-1的表达以及Wnt信号通路。在结肠癌标本中，miR-136表达水平与LRH-1 mRNA表达呈负相关。此外，LRH-1过表达部分逆转了miR-136在SW480和HCT116细胞系中诱导的抗肿瘤作用。综上所述，这些发现表明miR-136通过靶向LRH-1在结肠癌进展中发挥负调节作用，且miR-136下调导致LRH-1高表达和Wnt信号通路异常激活，这使得miR-136有可能成为结肠癌的潜在治疗靶点。
