title: MiR-503 inhibits hepatocellular carcinoma cell growth via inhibition of insulin-like growth factor 1 receptor.
abstract: MicroRNAs (miRs) have been demonstrated to play key roles in the development and progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism of miR-503 in HCC has not been fully uncovered. In this study, we found that miR-503 was significantly downregulated in HCC tissues compared to nontumorous liver tissues. Moreover, lower miR-503 levels were associated with the malignant progression of HCC, and the expression of miR-503 was also decreased in several common HCC cell lines compared to normal human liver cell line THLE-3. Overexpression of miR-503 inhibited proliferation but induced apoptosis of LM3 and HepG2 cells. Bioinformatical analysis and luciferase reporter assay further identified insulin-like growth factor 1 receptor (IGF-1R) as a novel target of miR-503 in 293T cells. Moreover, overexpression of miR-503 led to a significant decrease in the protein levels of IGF-1R, while knockdown of miR-503 enhanced its protein levels in LM3 and HepG2 cells. Besides, overexpression of IGF-1R reversed the effects of miR-503-mediated HCC cell proliferation and apoptosis, indicating that IGF-1R acts as a downstream effector of miR-503 in HCC cells. Furthermore, IGF-1R was found to be significantly upregulated in HCC tissues compared to nontumorous liver tissues. In addition, the mRNA levels of IGF-1R were inversely correlated to the miR-503 levels in the HCC tissues. Thus, we demonstrate that miR-503 inhibits the proliferation and induces the apoptosis of HCC cells, partly at least, by directly targeting IGF-1R, and suggest that IGF-1R may serve as a promising target for the treatment of HCC.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, People's Republic of China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Jiantai
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Liansheng
authors.initials: L
authors.lastname: Gong
keywords: apoptosis; hepatocellular carcinoma; insulin-like growth factor 1 receptor; microRNA-503; proliferation