Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Molecular therapy. Nucleic acids, 2015-12, Vol.4 (12), p.e270-e270, Article e270

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.