The tumor suppressor Sprouty2 is directly regulated by miR-21 and miR-27a in human hepatocellular carcinoma

DING Jie; HUANG Shenglin; LIANG Linhui; TIAN Qi; CHEN Taoyang; LI Jinjun; GU Jianren; HE Xianghuo

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The tumor suppressor Sprouty2 is directly regulated by miR-21 and miR-27a in human hepatocellular carcinoma

DING Jie 1,HUANG Shenglin 2 #,LIANG Linhui 2,TIAN Qi 2,CHEN Taoyang 3,LI Jinjun 2 #,GU Jianren 2 #,HE Xianghuo 2 *

1.State Key Laboratory of Oncogenes&Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032

2.State Key Laboratory of Oncogenes&Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

3.QiDong Liver Cancer Institute, Jiangsu, China

*Correspondence author

#Submitted by

Subject:

Funding: Doctoral Program of Higher Education of China Grant （No.No. 200802480076）

Opened online: 8 June 2012

Accepted by: none

Citation: DING Jie,HUANG Shenglin,LIANG Linhui.The tumor suppressor Sprouty2 is directly regulated by miR-21 and miR-27a in human hepatocellular carcinoma[OL]. [ 8 June 2012] http://en.paper.edu.cn/en_releasepaper/content/4479987

Sprouty2 (Spry2), a negative modulator of the Ras/ERK pathway, is frequently decreased in various cancers. However, the mechanism of Spry2 down-regulation in the malignancies is largely unknown. In current study, we demonstrated that Spry2 is directly regulated by microRNAs (miRNAs) and subsequently identified two oncogenic miRNA sequences miR-21 and miR-27a that directly target Spry2 expression. Furthermore, Spry2 exerts tumor suppressive effects and attenuates miR-21- and miR-27a-induced cell proliferation and migration in HCC cells. Moreover, Spry2 protein expression is inversely correlated with miR-21 and miR-27a expression, suggesting that loss of Spry2 may be due to elevated miR-21 and miR-27a expression in HCC. In conclusion, this study revealed a novel mechanism of Spry2 regulation at the post-transcriptional level in HCC. These findings will benefit the development of new Spry2-targeted therapeutics to treat HCC.

Keywords:hepatocellular carcinoma; microRNA; Tumor suppressor

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