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

• DOI: 10.18632/oncotarget.7292
• Publication Date: 2016-02-12T19:36:26Z
• Authors: Wei Sun; Zhuochao Zhang; Jianlin Wang; Runze Shang; Liang Zhou; Xing Wang; Juanli Duan; Bai Ruan; Yuan Gao; Bin Dai; Shibin Qu; Wei Liu; Rui Ding; Lin Wang; Desheng Wang; Kefeng Dou
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; MAP Kinase Signaling System; Liver Neoplasms; Mice, Nude; Middle Aged; Transfection; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Animals; Humans; Female; Neoplasm Metastasis; Extracellular Signal-Regulated MAP Kinases; Research Paper; Adaptor Proteins, Signal Transducing; Cell Proliferation

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.