IMR Press / FBL / Volume 24 / Issue 8 / DOI: 10.2741/4784

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
RICH2, a potential tumor suppressor in hepatocellular carcinoma
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1 The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710038, China
2 Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710038, China
3 Postdoctoral Research Station of Neurosurgery, Department of Neurosurgery, Wuhan General Hospital of PLA, Wuhan, Hubei 430070, China
4 Central Laboratory, Hainan Branch of PLA general Hospital, Sanya, Hainan 572013, China
5 Department of Convalescence, Aviation Medicine Appraisal and Training Centre, The Air Force, Hangzhou, Zhejiang 310007, China
6 Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710038, China
*Correspondence: zhangwei-7blk321@163.com (Wei Zhang)
Front. Biosci. (Landmark Ed) 2019, 24(8), 1363–1376; https://doi.org/10.2741/4784
Published: 1 June 2019
(This article belongs to the Special Issue Leader sequences of coronavirus are altered during infection)
Abstract

Rho GTPase-activating proteins (RhoGAPs) are implicated in the development and progression of hepatocellular carcinoma (HCC). We tested the idea that RICH2 is a tumor suppressor in HCC. Consistent with this, RICH2 was downregulated in HCC and HCC cell lines and RICH2 expression negatively correlated with the tumor size, TNM stage and metastasis in HCC. RICH2, in a Cdc42 dependent manner, regulated the formation of filopodia in HCC and stable overexpression of RICH2 significantly inhibited the clone formation, proliferation and invasion of HCC cells in vitro. Gene set enrichment analysis (GSEA) showed that the expression of RICH 2 positively correlated with the expression of WNT5a, that exert antagonistic effect on canonical WNT signalling whereas RICH2 expression inversely correlated with the expression of β-catenin (CTNNB1), that is involved in the proliferation and invasion HCC. These findings concurred with co-immunoprecipation of RICH2 with endogenous Cdc42, Rac1, and β-catenin. Finally, RICH2 overexpression suppressed tumor growth in vivo. The findings support the idea that RICH2 might act as a tumor suppressor in HCC.

Keywords
Filopodia
Hepatocellular Carcinoma
Rho GTPase
RICH2
WNT pathway
Figures
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