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Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the imp...

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Autores principales: Chai, Stella, Tong, Man, Ng, Kai Yu, Kwan, Pak Shing, Chan, Yuen Piu, Fung, Tsun Ming, Lee, Terence K., Wong, Nathalie, Xie, Dan, Yuan, Yun-Fei, Guan, Xin-Yuan, Ma, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170635/
https://www.ncbi.nlm.nih.gov/pubmed/25015418
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author Chai, Stella
Tong, Man
Ng, Kai Yu
Kwan, Pak Shing
Chan, Yuen Piu
Fung, Tsun Ming
Lee, Terence K.
Wong, Nathalie
Xie, Dan
Yuan, Yun-Fei
Guan, Xin-Yuan
Ma, Stephanie
author_facet Chai, Stella
Tong, Man
Ng, Kai Yu
Kwan, Pak Shing
Chan, Yuen Piu
Fung, Tsun Ming
Lee, Terence K.
Wong, Nathalie
Xie, Dan
Yuan, Yun-Fei
Guan, Xin-Yuan
Ma, Stephanie
author_sort Chai, Stella
collection PubMed
description Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC.
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spelling pubmed-41706352014-09-22 Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133 Chai, Stella Tong, Man Ng, Kai Yu Kwan, Pak Shing Chan, Yuen Piu Fung, Tsun Ming Lee, Terence K. Wong, Nathalie Xie, Dan Yuan, Yun-Fei Guan, Xin-Yuan Ma, Stephanie Oncotarget Research Paper Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC. Impact Journals LLC 2014-07-05 /pmc/articles/PMC4170635/ /pubmed/25015418 Text en Copyright: © 2014 Chai 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.
spellingShingle Research Paper
Chai, Stella
Tong, Man
Ng, Kai Yu
Kwan, Pak Shing
Chan, Yuen Piu
Fung, Tsun Ming
Lee, Terence K.
Wong, Nathalie
Xie, Dan
Yuan, Yun-Fei
Guan, Xin-Yuan
Ma, Stephanie
Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title_full Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title_fullStr Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title_full_unstemmed Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title_short Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
title_sort regulatory role of mir-142-3p on the functional hepatic cancer stem cell marker cd133
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170635/
https://www.ncbi.nlm.nih.gov/pubmed/25015418
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