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

Abstract

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.

• Authors: Stella Chai, Man Tong, Kai Yu Ng, Pak Shing Kwan, Yuen Piu Chan, Tsun Ming Fung, Terence K Lee, Nathalie Wong, Dan Xie, Yun-Fei Yuan, Xin-Yuan Guan, Stephanie Ma
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 14 Pg. 5725-35 (Jul 30 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25015418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AC133 Antigen
• Antigens, CD
• Glycoproteins
• MIRN142 microRNA, human
• MicroRNAs
• PROM1 protein, human
• Peptides
• Prom1 protein, mouse

Topics

• AC133 Antigen
• Animals
• Antigens, CD (metabolism)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Glycoproteins (metabolism)
• Hep G2 Cells
• Heterografts
• Humans
• Liver Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplastic Stem Cells (metabolism, pathology)
• Peptides (metabolism)
• Transfection