期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mtna.2015.47
关键词
miR-34a; non-small-cell lung cancer; RAD51; radiation
资金
- Doctors Cancer Foundation
- Lung Cancer Research Foundation
- Cancer Center Support (Core) Grant [CA016672]
- Mabuchi Research fund
- Orr Family Foundation
- MD Anderson Knowledge Gap award
- Department of Defense [W81XWH-06-1-0303, W81XWH-07-1-03060]
- Wiegand Foundation
- Cancer Prevention Research Institute of Texas (CPRIT)
- Lung Spore [5P50 CA070907]
- [R01 CA168484-02]
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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