miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally

Yi Zhang; Dayong Zheng; Yan Xiong; Chengbiao Xue; Gen Chen; Bibo Yan; Qifa Ye

doi:10.1016/j.febslet.2014.03.030

miR-202 suppresses cell proliferation in human hepatocellular carcinoma by downregulating LRP6 post-transcriptionally

FEBS Lett. 2014 May 21;588(10):1913-20. doi: 10.1016/j.febslet.2014.03.030. Epub 2014 Apr 3.

Authors

Yi Zhang¹, Dayong Zheng², Yan Xiong¹, Chengbiao Xue¹, Gen Chen¹, Bibo Yan¹, Qifa Ye³

Affiliations

¹ Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, PR China.
² Department of Oncology Nanfang Hosptial, Southern Medical University, Guangzhou 510515, PR China.
³ Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, PR China; The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, PR China. Electronic address: yqf_china@163.com.

PMID: 24704686
DOI: 10.1016/j.febslet.2014.03.030

Abstract

MicroRNAs have emerged as important regulators of carcinogenesis. In the current study, we observed that microRNA-202 (miR-202) is downregulated in hepatocellular carcinoma (HCC) cells and tissues, indicating a significant correlation between miR-202 expression and HCC progression. Overexpression of miR-202 in HCC cells suppressed cell proliferation and tumorigenicity, while downregulation of miR-202 enhanced the cells' proliferative capacity. Furthermore, we identified low-density lipoprotein receptor-related protein 6 (LRP6) as a direct target of miR-202. miR-202 suppresses the expression of LRP6 by binding to the 3'-untranslated region (UTR) of its mRNA. Finally, we found that silencing the expression of LRP6 is the essential biological function of miR-202 during HCC cell proliferation. Collectively, our findings reveal that miR-202 is a potential tumor suppressive miRNA that participates in carcinogenesis of human HCC by suppressing LRP6 expression.

Keywords: Hepatocellular carcinoma; Proliferation; lipoprotein receptor-related protein 6; microRNA-202.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions / genetics
Blotting, Western
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line
Cell Line, Tumor
Cell Proliferation*
Down-Regulation
Gene Expression Regulation, Neoplastic*
Hep G2 Cells
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Low Density Lipoprotein Receptor-Related Protein-6 / genetics*
Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
MicroRNAs / genetics*
MicroRNAs / metabolism
RNA Interference
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction

Substances

3' Untranslated Regions
LRP6 protein, human
Low Density Lipoprotein Receptor-Related Protein-6
MIRN202 microRNA, human
MicroRNAs
RNA, Messenger