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HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma

HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present...

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Autores principales: YANG, HAIXIA, ZHOU, JIUPENG, MI, JIANQIANG, MA, KE, FAN, YANGWEI, NING, JING, WANG, CHUYING, WEI, XIN, ZHAO, HUADONG, LI, ENXIAO
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564083/
https://www.ncbi.nlm.nih.gov/pubmed/26260613
http://dx.doi.org/10.3892/or.2015.4194
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author YANG, HAIXIA
ZHOU, JIUPENG
MI, JIANQIANG
MA, KE
FAN, YANGWEI
NING, JING
WANG, CHUYING
WEI, XIN
ZHAO, HUADONG
LI, ENXIAO
author_facet YANG, HAIXIA
ZHOU, JIUPENG
MI, JIANQIANG
MA, KE
FAN, YANGWEI
NING, JING
WANG, CHUYING
WEI, XIN
ZHAO, HUADONG
LI, ENXIAO
author_sort YANG, HAIXIA
collection PubMed
description HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC.
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spelling pubmed-45640832015-11-30 HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma YANG, HAIXIA ZHOU, JIUPENG MI, JIANQIANG MA, KE FAN, YANGWEI NING, JING WANG, CHUYING WEI, XIN ZHAO, HUADONG LI, ENXIAO Oncol Rep Articles HOXD10, a key regulator of cell-differentiated phenotype maintainence, has been demonstrated to be involved in the tumorigenesis of many human malignacies. However, the status of HOXD10 expression and its biological function in cholangiocellular carcinoma (CCC) remain to be clarified. In the present study, we investigated the clinical significance and biological functions of HOXD10 in CCC and found that the expression of HOXD10 and its downstream effector RHOC was significantly different in well-differentiated CCC tissues compared with poorly-differentiated lesions. We also observed a significant correlation between low HOXD10 and high RHOC expression levels and worse prognosis. The stable overexpression of HOXD10 by lentivirus vector significantly inhibited cell invasion partly by downregulating the expression of MMP2 and MMP9, and significantly increased early apoptosis in CCC cell lines and induced G1 phase cell cycle arrest, contributing to the inhibition of cell proliferation in vitro. Additionally, we demonstrated that the inactivation of the RHOC/AKT/MAPK pathway was involved in the tumor-suppressive functions of HOXD10 in CCC. These results suggested that HOXD10 may be a putative suppressor gene and can act as a prognostic marker and potentially a novel therapeutic target for CCC. D.A. Spandidos 2015-10 2015-08-10 /pmc/articles/PMC4564083/ /pubmed/26260613 http://dx.doi.org/10.3892/or.2015.4194 Text en Copyright: © Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
YANG, HAIXIA
ZHOU, JIUPENG
MI, JIANQIANG
MA, KE
FAN, YANGWEI
NING, JING
WANG, CHUYING
WEI, XIN
ZHAO, HUADONG
LI, ENXIAO
HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title_full HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title_fullStr HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title_full_unstemmed HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title_short HOXD10 acts as a tumor-suppressive factor via inhibition of the RHOC/AKT/MAPK pathway in human cholangiocellular carcinoma
title_sort hoxd10 acts as a tumor-suppressive factor via inhibition of the rhoc/akt/mapk pathway in human cholangiocellular carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564083/
https://www.ncbi.nlm.nih.gov/pubmed/26260613
http://dx.doi.org/10.3892/or.2015.4194
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