Oncotarget

Research Papers:

miR-564 inhibits hepatocellular carcinoma cell proliferation and invasion by targeting the GRB2-ERK1/2-AKT axis

Chaojie Liang, Yingchen Xu, Hua Ge, Bingchen Xing, Guanqun Li, Guangming Li and Jixiang Wu _

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Oncotarget. 2017; 8:107543-107557. https://doi.org/10.18632/oncotarget.22504

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Abstract

Chaojie Liang1,*, Yingchen Xu1,*, Hua Ge1, Bingchen Xing1, Guanqun Li1, Guangming Li1 and Jixiang Wu1

1Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Dongcheng, Beijing 100730, China

*These authors are contributed equally to this work

Correspondence to:

Jixiang Wu, email: trwujixiang2016@126.com

Guangming Li, email: liguangming2016@126.com

Keywords: miR-564; HCC; GRB2; PI3K/AKT; ERK1/2

Received: August 21, 2017     Accepted: October 28, 2017     Published: November 18, 2017

ABSTRACT

Recent studies have shown that miR-564 is closely related to the development of various tumors, including breast cancer, lung cancer and glioma. However, few studies have examined miR-564 in hepatocellular carcinoma (HCC). Here, we demonstrated that miR-564 expression in HCC tissues was lower than that in adjacent noncancerous tissues and that miR-564 expression was associated with tumor size, tumor number and vein invasion. Bioinformatics analyses showed that low levels of miR-564 were correlated with poor prognosis. Furthermore, upregulation of miR-564 impaired SMCC7721 and MHCC97H cell proliferation, migration and invasion in vitro and reduced tumorigenesis in vivo. Next, we found that GRB2 was a direct target gene of miR-564 in the HCC cell lines. GRB2 was highly expressed in HCC tissues and negatively correlated with miR-564 expression levels. When GRB2 was downregulated by GRB2-siRNA, HCC cell proliferation, invasion and metastasis were impaired, and restoring GRB2 expression partially reversed the inhibitory effects of miR-564. Western blot analysis showed that miR-564 overexpression reduced GRB2 expression in HCC cell lines and inhibited ERK1/2 and AKT phosphorylation. miR-564 overexpression also upregulated the epithelial-like cell marker E-cadherin and downregulated the interstitial cell-like markers N-cadherin and vimentin. These results suggest that miR-564 inhibits the malignant phenotype of HCC cells by targeting the GRB2-ERK1/2-AKT axis. Consequently, miR-564 may be used as a prognostic marker and therapeutic target for HCC.


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