@article{857d2458e08443e0a81aa5950279275d,
title = "MiR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13",
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.",
author = "Peijing Zhang and Li Wang and Cristian Rodriguez-Aguayo and Yuan Yuan and Debeb, {Bisrat G.} and Dahu Chen and Yutong Sun and You, {M. James} and Yongqing Liu and Dean, {Douglas C.} and Woodward, {Wendy A.} and Han Liang and Xianbin Yang and Gabriel Lopez-Berestein and Sood, {Anil K.} and Ye Hu and Ang, {K. Kian} and Junjie Chen and Li Ma",
note = "Funding Information: We thank the shRNA and ORFeome Core (supported by the core grant P30CA016672 from NIH) at MD Anderson Cancer Center and Drs Z. Gong, J. Yuan and A. Lin for reagents and technical assistance. We thank members of the Ma Laboratory for discussion. This work is supported by NIH grants R00CA138572 (to L.M.), R01CA166051 (to L.M.), R01CA181029 (to L.M.), R44GM086937 (to X.Y.) and R43GM100777 (to X.Y.) and a CPRIT Scholar Award R1004 (to L.M.). L.M. is a R. Lee Clark Fellow of The University of Texas MD Anderson Cancer Center. M.J.Y. is supported in part by NIH R01CA164346, Developmental Research Award in Leukemia SPORE CA100632, Center for Inflammation and Cancer, Center for Genetics and Genomics, Institutional Research Grant and Sister Institution Network fund of MD Anderson Cancer Center. L.W. and K.K.A. are supported by the Cancer Center Support Grant P30CA016672 and the Gilbert H. Fletcher Chair. B.G.D. and W.A.W. are supported by a Komen Foundation Grant KG101478. Y.H. is supported in part by NIH U54CA151668. We wish to dedicate this work to the memory of Dr K. Kian Ang. Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",
year = "2014",
doi = "10.1038/ncomms6671",
language = "English (US)",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}