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

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...

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Detalles Bibliográficos
Autores principales: Cortez, Maria Angelica, Valdecanas, David, Niknam, Sharareh, Peltier, Heidi J, Diao, Lixia, Giri, Uma, Komaki, Ritsuko, Calin, George A, Gomez, Daniel R, Chang, Joe Y, Heymach, John Victor, Bader, Andreas G, Welsh, James William
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014539/
https://www.ncbi.nlm.nih.gov/pubmed/26670277
http://dx.doi.org/10.1038/mtna.2015.47
Descripción
Sumario: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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