MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
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Wei Sun1,*, Zhuochao Zhang1,*, Jianlin Wang1,*, Runze Shang1, Liang Zhou2, Xing Wang1, Juanli Duan1, Bai Ruan1, Yuan Gao3, Bin Dai1, Shibin Qu1, Wei Liu1, Rui Ding1, Lin Wang1, Desheng Wang1, Kefeng Dou1
1Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China
2Department of General Surgery, The 155th Central Hospital of PLA, Kaifeng, Henan, China
3Department of Hepatobiliary Surgery, The 224th Hospital of PLA, Jiamusi, Heilongjiang, China
*These authors have contributed equally to this work
Kefeng Dou, e-mail: firstname.lastname@example.org
Desheng Wang, e-mail: email@example.com
Lin Wang, e-mail: firstname.lastname@example.org
Keywords: hepatocellular carcinoma, miR-150, GAB1, epithelial mesenchymal transition, metastasis
Received: October 27, 2015 Accepted: January 27, 2016 Published: February 9, 2016
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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