@article{05055215929d4273ae8f84e85866ae89,
title = "In vivo delivery of miR-34a sensitizes lung tumors to radiation through RAD51 regulation",
abstract = "MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC), among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3′ untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.",
keywords = "Non-small-cell Lung cancer, RAD51, Radiation, miR-34a",
author = "Cortez, {Maria Angelica} and David Valdecanas and Sharareh Niknam and Peltier, {Heidi J.} and Lixia Diao and Uma Giri and Ritsuko Komaki and Calin, {George A.} and Gomez, {Daniel R.} and Chang, {Joe Y.} and Heymach, {John Victor} and Bader, {Andreas G.} and Welsh, {James William}",
note = "Funding Information: The authors thank Christine F Wogan, MS, ELS, of MD Anderson's Division of Radiation Oncology, for editorial contributions; Jeffrey D. Parvin, Ohio State University, Columbus, OH, for sharing the HeLa-DR cells and the plasmid expressing the I-SceI endonuclease; and Kevin Kelnar for providing materials from Mirna to MD Anderson. This work was supported by Doctors Cancer Foundation Grant; The Lung Cancer Research Foundation; Cancer Center Support (Core) Grant CA016672 to The University of Texas MD Anderson Cancer Center; the Mabuchi Research fund; the family of M. Adnan Hamed and the Orr Family Foundation to MD Anderson Cancer Center's Thoracic Radiation Oncology program; an MD Anderson Knowledge Gap award; Department of Defense (BATTLE award W81XWH-06-1-0303, PROSPECT award W81XWH-07-1-03060); and the Wiegand Foundation. H.J.P. and A.G.B. were supported by a commercialization grant from the Cancer Prevention Research Institute of Texas (CPRIT). J.V.H. is supported by R01 CA168484-02 and the Lung Spore 5P50 CA070907. The authors declared no conflict of interest.",
year = "2015",
month = dec,
doi = "10.1038/mtna.2015.47",
language = "English (US)",
volume = "4",
pages = "e270",
journal = "Molecular Therapy - Nucleic Acids",
issn = "2162-2531",
publisher = "Nature Publishing Group",
number = "12",
}