MicroRNA-185 inhibits cell proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Six2.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) plays an important role in the malignant transformation of cancer. MicroRNAs are a group of small non-coding RNA molecules that down-regulate the expression of genes involved in tumorigenesis. Although microRNA-185 (miR-185) participates in the pathogenesis of several types of cancer, its relationship with EMT in human hepatocellular carcinoma (HCC) has not been investigated. The present study aims to elucidate the regulatory effects of miR-185 on EMT in HCC cells. MATERIALS AND METHODS: MTT and an in vitro wound-healing assay were performed to determine cell growth and metastasis potential, respectively. Real-time PCR was used to measure the mRNA expression of miR-185 and Six2. In addition, protein expression levels of Six2 and EMT-related markers were determined by western blot. RESULTS: Our study showed that miR-185 was significantly down-regulated in HCC cells. Also, a luciferase reporter gene assay confirmed Six2 as a direct target of miR-185. Functional analyses indicated that miR-185 up-regulation remarkably suppressed cell growth and the metastatic potential of HCC cells. We also found that ectopic expression of miR-185 reversed EMT via the up-regulation of E-cadherin and down-regulation of vimentin in epithelial and mesenchymal HCC cells. CONCLUSIONS: miR-185 suppresses cell growth and EMT progression by targeting Six2, European Review for Medical and Pharmacological Sciences MicroRNA-185 inhibits cell proliferation and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting Six2 S.-M. ZHU1, C.-M. CHEN2, Z.-Y. JIANG3, B. YUAN4, M. JI5, F.-H. WU6, J. JIN6 1Department of Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China 2Information Center, The First Affiliated of Chongqing Medical University, Chongqing, China 3Cancer Center, Zhejiang Quhua Hospital, Quzhou, Zhejiang, China 4Department of Pharmacy, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 5Yang Pu District Hospital of Traditional Chinese Medical, Shanghai, China; 6Department of Pharmacy, Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Song-ming Zhu, Chi-mei Chen, Zhong-yu Jiang and Bo Yuan are the co-first authors providing a novel target for the molecular treatment of liver malignancies. [ABSTRACT FROM AUTHOR]