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Molecular Cancer
Published in: Molecular Cancer 1/2015

Open Access 01-12-2015 | Research

Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of hepatocellular carcinoma cells

Authors: Jialin He, Kai Zhao, Lu Zheng, Zhizhen Xu, Wei Gong, Shan Chen, Xiaodong Shen, Gang Huang, Min Gao, Yijun Zeng, Yan Zhang, Fengtian He

Published in: Molecular Cancer | Issue 1/2015

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Abstract

Background

microRNA-122 (miR-122) is the most abundant and specific miRNA in the liver. It acts as an important tumor suppressor in hepatocellular carcinoma (HCC) through regulating its target genes, but details of its own regulation are largely unknown. Farnesoid X receptor (FXR), a transcription factor with multiple functions, plays an important role in protecting against liver carcinogenesis, but it is unclear whether the anti-HCC effect of FXR is involved in the regulation of miR-122.

Methods

The levels of miR-122 and FXR in HCC tissues and cell lines were examined by quantitative real-time PCR (qRT-PCR). qRT-PCR was also used to detect the expression of miR-122 target genes at mRNA level, while Western blotting was used to analyze that of their protein products. The effect of FXR on the transcriptional activity of miR-122 promoter was evaluated by a luciferase reporter assay. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were performed to identify the FXR binding site within miR-122 promoter region. The cell proliferation was analyzed by a CCK-8 assay. The influence of FXR on tumor growth and miR-122 expression in vivo was monitored using HCC xenografts in nude mice.

Results

The expression of FXR was positively correlated with that of miR-122 in HCC tissues and cell lines. Activation of FXR in HCC cells upregulated miR-122 expression and in turn downregulated the expression of miR-122 target genes including insulin-like growth factor-1 receptor and cyclin G1. FXR bound directly to the DR2 element (−338 to −325) in miR-122 promoter region, and enhanced the promoter’s transcriptional activity. Functional experiments showed that the FXR-mediated upregulation of miR-122 suppressed the proliferation of HCC cells in vitro and the growth of HCC xenografts in vivo.

Conclusions

miR-122 is a novel target gene of FXR, and the upregulation of miR-122 by FXR represses the growth of HCC cells, suggesting that FXR may serve as a key transcriptional regulator for manipulating miR-122 expression, and the FXR/miR-122 pathway may therefore be a novel target for the treatment of HCC.
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Metadata
Title
Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of hepatocellular carcinoma cells
Authors
Jialin He
Kai Zhao
Lu Zheng
Zhizhen Xu
Wei Gong
Shan Chen
Xiaodong Shen
Gang Huang
Min Gao
Yijun Zeng
Yan Zhang
Fengtian He
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2015
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-015-0427-9

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