MiR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13

Peijing Zhang, Li Wang, Cristian Rodriguez-Aguayo, Yuan Yuan, Bisrat G. Debeb, Dahu Chen, Yutong Sun, M. James You, Yongqing Liu, Douglas C. Dean, Wendy A. Woodward, Han Liang, Xianbin Yang, Gabriel Lopez-Berestein, Anil K. Sood, Ye Hu, K. Kian Ang, Junjie Chen, Li Ma

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Tumour cells associated with therapy resistance (radioresistance and drug resistance) are likely to give rise to local recurrence and distant metastatic relapse. Recent studies revealed microRNA (miRNA)-mediated regulation of metastasis and epithelial-mesenchymal transition; however, whether specific miRNAs regulate tumour radioresistance and can be exploited as radiosensitizing agents remains unclear. Here we find that miR-205 promotes radiosensitivity and is downregulated in radioresistant subpopulations of breast cancer cells, and that loss of miR-205 is highly associated with poor distant relapse-free survival in breast cancer patients. Notably, therapeutic delivery of miR-205 mimics via nanoliposomes can sensitize the tumour to radiation in a xenograft model. Mechanistically, radiation suppresses miR-205 expression through ataxia telangiectasia mutated (ATM) and zinc finger E-box binding homeobox 1 (ZEB1). Moreover, miR-205 inhibits DNA damage repair by targeting ZEB1 and the ubiquitin-conjugating enzyme Ubc13. These findings identify miR-205 as a radiosensitizing miRNA and reveal a new therapeutic strategy for radioresistant tumours.

Original languageEnglish (US)
Article number5671
JournalNature communications
Volume5
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zhang, P., Wang, L., Rodriguez-Aguayo, C., Yuan, Y., Debeb, B. G., Chen, D., Sun, Y., You, M. J., Liu, Y., Dean, D. C., Woodward, W. A., Liang, H., Yang, X., Lopez-Berestein, G., Sood, A. K., Hu, Y., Ang, K. K., Chen, J., & Ma, L. (2014). MiR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13. Nature communications, 5, [5671]. https://doi.org/10.1038/ncomms6671