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Mol Ther Nucleic Acids. 2015 Dec 15;4:e270. doi: 10.1038/mtna.2015.47.

In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation.

Author information

1
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
2
Mirna Therapeutics, Inc., Austin, Texas, USA.
3
Department of Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

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.

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