Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133
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Stella Chai1,*, Man Tong1,*, Kai Yu Ng1,*, Pak Shing Kwan2, Yuen Piu Chan3, Tsun Ming Fung1, Terence K. Lee3,4,5, Nathalie Wong6, Dan Xie7, Yun-Fei Yuan7, Xin-Yuan Guan2,4,5 and Stephanie Ma1,4,5
1 Department of Anatomy, The University of Hong Kong, Hong Kong
2 Department of Clinical Oncology, The University of Hong Kong, Hong Kong
3 Departments of Pathology, The University of Hong Kong, Hong Kong
4 State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong
5 Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
6 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong
7 State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Centre, Guangzhou, China
* These authors contributed equally to the work
Stephanie Ma, email:
Keywords: CD133; miR-142-3p; tumor-initiating cells
Received: June 2, 2014 Accepted: July 3, 2014 Published: July 5, 2014
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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