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MicroRNA-135a-induced formation of CD133+ subpopulation with cancer stem cell properties in cervical cancer.

Authors
  • Leung, Carmen O N1
  • Deng, Wen2
  • Ye, Tian-Min3, 1
  • Ngan, Hextan Y S1
  • Tsao, Sai Wah4
  • Cheung, Annie N Y5
  • Ziru, Niu1
  • Yuen, Dominic C K1
  • Pang, Ronald T K1, 6
  • Yeung, William S B3, 1, 6
  • 1 Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong Special Administrative Region. , (Hong Kong SAR China)
  • 2 School of Nursing, The University of Hong Kong, Hong Kong Special Administrative Region. , (Hong Kong SAR China)
  • 3 Shenzhen Key Laboratory of Fertility Regulation, Shenzhen, People's Republic of China. , (China)
  • 4 School of Biomedical Sciences, The University of Hong Kong, Hong Kong Special Administrative Region. , (Hong Kong SAR China)
  • 5 Department of Pathology, The University of Hong Kong, Hong Kong Special Administrative Region. , (Hong Kong SAR China)
  • 6 Centre for Reproduction, Development and Growth, The University of Hong Kong, Hong Kong Special Administrative Region. , (Hong Kong SAR China)
Type
Published Article
Journal
Carcinogenesis
Publisher
Oxford University Press
Publication Date
Nov 13, 2020
Volume
41
Issue
11
Pages
1592–1604
Identifiers
DOI: 10.1093/carcin/bgaa025
PMID: 32415843
Source
Medline
Language
English
License
Unknown

Abstract

Cancer stem cells (CSCs) play significant roles in tumor initiation. MicroRNA-135a (miR-135a) induced the formation of a CD133+ subpopulation from a human papillomavirus-immortalized cervical epithelial cell line. Compared with the CD133- cells, the CD133+ cells expressed higher levels of miR-135a and OCT4, exhibited significantly higher tumorsphere forming capacity and the time required for tumorsphere formation was shortened in the second generation. Serum induction suppressed the expression of CD133, OCT4 and miR-135a, but increased expression of involucrin in the miR-135a-induced CD133+ cells. The miR-135a-induced CD133+ cells were tumorigenic in a limiting dilution approach in vivo. The cells expressed significantly higher level of active β-catenin and OCT4 than the CD133- counterpart. Wnt3a enhanced the expression of OCT4 and CD133 in cervical cancer cells but failed to enhance CD133 transcription in normal cervical cells. Wnt3a stimulation also increased tumorsphere size and self-renewal of miR-135a-induced CD133+ subpopulation. Wnt/β-catenin inhibition suppressed tumorsphere formation while Wnt3a partially nullified the inhibitory effect. Taken together, miR-135a induced the formation of a subpopulation of cells with CSC properties both in vitro and in vivo and the Wnt/β-catenin signaling pathway is essential to maintain its tumorigenicity. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

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