title: 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.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong.
authors.forename: Stella
authors.initials: S
authors.lastname: Chai
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong.
authors.forename: Man
authors.initials: M
authors.lastname: Tong
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong.
authors.forename: Kai Yu
authors.initials: KY
authors.lastname: Ng
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Hong Kong.
authors.forename: Pak Shing
authors.initials: PS
authors.lastname: Kwan
authors.affiliation: Departments of Pathology, The University of Hong Kong, Hong Kong.
authors.forename: Yuen Piu
authors.initials: YP
authors.lastname: Chan
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong.
authors.forename: Tsun Ming
authors.initials: TM
authors.lastname: Fung
authors.affiliation: Departments of Pathology, The University of Hong Kong, Hong Kong. State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Terence K
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Centre, Guangzhou, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Hong Kong. State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong. State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ma
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism*; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D014162:Transfection
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse