MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis

// Wei Sun 1, * , Zhuochao Zhang 1, * , Jianlin Wang 1, * , Runze Shang 1 , Liang Zhou 2 , Xing Wang 1 , Juanli Duan 1 , Bai Ruan 1 , Yuan Gao 3 , Bin Dai 1 , Shibin Qu 1 , Wei Liu 1 , Rui Ding 1 , Lin Wang 1 , Desheng Wang 1 , Kefeng Dou 1 1 Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China 2 Department of General Surgery, The 155th Central Hospital of PLA, Kaifeng, Henan, China 3 Department of Hepatobiliary Surgery, The 224th Hospital of PLA, Jiamusi, Heilongjiang, China * These authors have contributed equally to this work Correspondence to: Kefeng Dou, e-mail: [email protected] Desheng Wang, e-mail: [email protected] Lin Wang, e-mail: [email protected] Keywords: hepatocellular carcinoma, miR-150, GAB1, epithelial mesenchymal transition, metastasis Received: October 27, 2015      Accepted: January 27, 2016      Published: February 9, 2016 ABSTRACT MicroRNA-150 (miR-150) is frequently dysregulated in cancer and is involved in carcinogenesis and cancer progression. In this study, we found that miR-150 was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent noncancerous tissues. Low levels of miR-150 were significantly associated with worse clinicopathological characteristics and a poor prognosis for patients with HCC. miR-150 overexpression inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo . Further experiments indicated that Grb2-associated binding protein 1 (GAB1) was a direct target of miR-150 in HCC cells. In addition, GAB1 expression was increased in HCC tissues and inversely correlated with miR-150 levels. Knockdown of GAB1 mimicked the tumor-suppressive effects of miR-150 overexpression on HCC cells, whereas restoration of GAB1 expression partially abolished the inhibitory effects. Moreover, miR-150 overexpression decreased GAB1 expression, subsequently downregulated phospho-ERK1/2 and suppressed epithelial-mesenchymal-transition (EMT). These effects caused by miR-150 overexpression were alleviated by exogenous GAB1 expression. Taken together, this study demonstrates that miR-150 may be useful as a prognostic marker and that the identified miR-150-GAB1-ERK axis is a potential therapeutic target for HCC.

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