Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells

Adult hepatic progenitor cells (HPCs) are involved in a wide range of human liver diseases, including hepatocellular carcinoma (HCC). Bmi1 has been reported to have vital roles in stem cell self-renewal and carcinogenesis. We have previously demonstrated that Bmi1 is upregulated in HCC with bile duc...

Full description

Bibliographic Details
Main Authors:	Zhang, R, Wu, W R, Shi, X D, Xu, L B, Zhu, M S, Zeng, H, Liu, C
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154353/

id	pubmed-5154353
recordtype	oai_dc
spelling	pubmed-51543532016-12-21 Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells Zhang, R Wu, W R Shi, X D Xu, L B Zhu, M S Zeng, H Liu, C Original Article Adult hepatic progenitor cells (HPCs) are involved in a wide range of human liver diseases, including hepatocellular carcinoma (HCC). Bmi1 has been reported to have vital roles in stem cell self-renewal and carcinogenesis. We have previously demonstrated that Bmi1 is upregulated in HCC with bile duct tumor thrombi, a subtype of HCC characterized by profuse expression of hepatic stem cell markers. However, the function of Bmi1 in HPCs has not yet been well elucidated. The current study was designed to investigate the effects of Bmi1 on the biological properties of rat HPCs. To accomplish this, Bmi1 was silenced or enhanced in two HPC cell lines (WB-F344 and OC3) by, respectively, using either small interfering RNA against Bmi1 or a forced Bmi1 expression retroviral vector. The biological functions of Bmi1 in HPCs were investigated through cell proliferation assays, colony-formation assays, cell cycle analysis and invasion assays, as well as through xenograft-formation assays. In this study, genetic depletion of Bmi1 repressed cell proliferation, colony formation and invasion in both assessed HPC cell lines relative to controls. Conversely, forced expression of Bmi1 in two HPCs cell lines promoted cell proliferation, colony formation and invasion in vitro. Aldehyde dehydrogenase (ALDH) assay revealed a significant increase in the number of ALDH-positive cells following the forced expression of Bmi1 in HPCs. Most importantly, transplantation of forced Bmi1 expression HPCs into nude mice resulted in the formation of tumors with histological features of poorly differentiated HCC. Taken together, our findings indicate that forced expression of Bmi1 promotes the malignant transformation of HPCs, suggesting Bmi1 might be a potential molecular target for the treatment of HCC. Nature Publishing Group 2016-02 2016-02-29 /pmc/articles/PMC5154353/ /pubmed/26926789 http://dx.doi.org/10.1038/oncsis.2016.6 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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	Zhang, R Wu, W R Shi, X D Xu, L B Zhu, M S Zeng, H Liu, C
spellingShingle	Zhang, R Wu, W R Shi, X D Xu, L B Zhu, M S Zeng, H Liu, C Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
author_facet	Zhang, R Wu, W R Shi, X D Xu, L B Zhu, M S Zeng, H Liu, C
author_sort	Zhang, R
title	Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
title_short	Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
title_full	Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
title_fullStr	Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
title_full_unstemmed	Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells
title_sort	dysregulation of bmi1 promotes malignant transformation of hepatic progenitor cells
description	Adult hepatic progenitor cells (HPCs) are involved in a wide range of human liver diseases, including hepatocellular carcinoma (HCC). Bmi1 has been reported to have vital roles in stem cell self-renewal and carcinogenesis. We have previously demonstrated that Bmi1 is upregulated in HCC with bile duct tumor thrombi, a subtype of HCC characterized by profuse expression of hepatic stem cell markers. However, the function of Bmi1 in HPCs has not yet been well elucidated. The current study was designed to investigate the effects of Bmi1 on the biological properties of rat HPCs. To accomplish this, Bmi1 was silenced or enhanced in two HPC cell lines (WB-F344 and OC3) by, respectively, using either small interfering RNA against Bmi1 or a forced Bmi1 expression retroviral vector. The biological functions of Bmi1 in HPCs were investigated through cell proliferation assays, colony-formation assays, cell cycle analysis and invasion assays, as well as through xenograft-formation assays. In this study, genetic depletion of Bmi1 repressed cell proliferation, colony formation and invasion in both assessed HPC cell lines relative to controls. Conversely, forced expression of Bmi1 in two HPCs cell lines promoted cell proliferation, colony formation and invasion in vitro. Aldehyde dehydrogenase (ALDH) assay revealed a significant increase in the number of ALDH-positive cells following the forced expression of Bmi1 in HPCs. Most importantly, transplantation of forced Bmi1 expression HPCs into nude mice resulted in the formation of tumors with histological features of poorly differentiated HCC. Taken together, our findings indicate that forced expression of Bmi1 promotes the malignant transformation of HPCs, suggesting Bmi1 might be a potential molecular target for the treatment of HCC.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154353/
_version_	1613778557808410624

Dysregulation of Bmi1 promotes malignant transformation of hepatic progenitor cells

Similar Items