MicroRNA-492 expression promotes the progression of hepatic cancer by targeting PTEN

Cancer Cell International

Chengyi Sun¹  Yaozheng Pan¹  Zhipeng Li¹  Chao Yu¹  Yi Zhang²  Jianxin Jiang¹ 

[1] Department of Biliary-Hepatic Surgery, Affiliated Hospital of Guiyang Medical College, 28 Guiyi Road, Guiyang 550001, Guizhou, China;Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Wuhan 430071, Hubei, China

关键词: AKT;    PTEN;    Hepatocellular carcinoma;    microRNA;   

Others  :  1121659
DOI  :  10.1186/s12935-014-0095-7

 received in 2014-02-28, accepted in 2014-09-09,  发布年份 2014

【 摘 要 】

Background

Aberrant microRNA (miRNA) expression plays an essential role in the pathogenesis of Hepatocellular Carcinoma (HCC). However, specific involvement of miRNAs in HCC remains incompletely understood. The aim of this study was to explore the relevant microRNAs involved in the development of HCC.

Methods

MicroRNA microarray was used to screen for the differentially expressed miRNAs in cancerous tissue and adjacent non-cancerous control tissue from patients with HCC (n = 3). Quantitative PCR was subsequently used to verify the results of microarray. Based on the findings, we investigated the role of miR-492 in the pathogenesis of HCC in vitro and in vivo using three tumor cells lines. Furthermore, we analyzed the clinical correlation of miR-492 expression with patient survival (n = 28).

Results

We showed that microRNA-492 (miR-492) was elevated in HCC samples from patients with hepatic cancer. Knockdown of miR-492 attenuated the proliferation of cancer cell lines in vitro and inhibited primary tumor growth in vivo in SCID mice. We identified PTEN as a functional target for miR-492. Overexpression of miR-492 resulted in decreased PTEN expression and was associated with increased AKT activation in cancer cell lines. Moreover, miR-492-mediated increase of the proliferation of cancer cells was able to be suppressed by a PI3K inhibitor and an AKT inhibitor. The HCC patients with high miR-492/low PTEN had poorer survival.

Conclusions

miR-492 is implicated in the regulation of HCC progression through PTEN and AKT pathway. The data suggest that miR-492 is a biomarker of HCC and a potential therapeutic target for hepatocellular carcinoma.

【 授权许可】

   
2014 Jiang et al.; licensee BioMed Central Ltd.

【 图 表 】

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