| Autor: |
Maria Angelica Cortez, David Valdecanas, Sharareh Niknam, Heidi J Peltier, Lixia Diao, Uma Giri, Ritsuko Komaki, George A Calin, Daniel R Gomez, Joe Y Chang, John Victor Heymach, Andreas G Bader, James William Welsh |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 4, Iss C (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1038/mtna.2015.47 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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