miR-205 acts as a tumor radiosensitizer by targeting ZEB1 and Ubc13

Zhang P1, Wang L, Rodriguez-Aguayo C, Yuan Y, Debeb BG, Chen D, Sun Y, You MJ, Liu Y, Dean DC, Woodward WA, Liang H, Yang X, Lopez-Berestein G, Sood AK, Hu Y, Ang KK, Chen J, Ma L
Source: Nat Commun.
Publication Date: (2014)
Issue: 5(5): 5671
Research Area:
Cancer Research/Cell Biology
Basic Research
Cells used in publication:
Species: human
Tissue Origin: breast
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.