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

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

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 s...

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Main Authors: Sun, Wei, Zhang, Zhuochao, Wang, Jianlin, Shang, Runze, Zhou, Liang, Wang, Xing, Duan, Juanli, Ruan, Bai, Gao, Yuan, Dai, Bin, Qu, Shibin, Liu, Wei, Ding, Rui, Wang, Lin, Wang, Desheng, Dou, Kefeng
Format: Online
Language:English
Published: Impact Journals LLC 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905496/
id pubmed-4905496
recordtype oai_dc
spelling pubmed-49054962016-06-24 MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis Sun, Wei Zhang, Zhuochao Wang, Jianlin Shang, Runze Zhou, Liang Wang, Xing Duan, Juanli Ruan, Bai Gao, Yuan Dai, Bin Qu, Shibin Liu, Wei Ding, Rui Wang, Lin Wang, Desheng Dou, Kefeng Research Paper 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. Impact Journals LLC 2016-02-09 /pmc/articles/PMC4905496/ /pubmed/26871477 http://dx.doi.org/10.18632/oncotarget.7292 Text en Copyright: © 2016 Sun et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Sun, Wei
Zhang, Zhuochao
Wang, Jianlin
Shang, Runze
Zhou, Liang
Wang, Xing
Duan, Juanli
Ruan, Bai
Gao, Yuan
Dai, Bin
Qu, Shibin
Liu, Wei
Ding, Rui
Wang, Lin
Wang, Desheng
Dou, Kefeng
spellingShingle Sun, Wei
Zhang, Zhuochao
Wang, Jianlin
Shang, Runze
Zhou, Liang
Wang, Xing
Duan, Juanli
Ruan, Bai
Gao, Yuan
Dai, Bin
Qu, Shibin
Liu, Wei
Ding, Rui
Wang, Lin
Wang, Desheng
Dou, Kefeng
MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
author_facet Sun, Wei
Zhang, Zhuochao
Wang, Jianlin
Shang, Runze
Zhou, Liang
Wang, Xing
Duan, Juanli
Ruan, Bai
Gao, Yuan
Dai, Bin
Qu, Shibin
Liu, Wei
Ding, Rui
Wang, Lin
Wang, Desheng
Dou, Kefeng
author_sort Sun, Wei
title MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
title_short MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
title_full MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
title_fullStr MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
title_full_unstemmed MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis
title_sort microrna-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the gab1-erk axis
description 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.
publisher Impact Journals LLC
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905496/
_version_ 1613593775965208576

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