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

被引：69

作者：

Cortez, Maria Angelica ^{[1
]}

Valdecanas, David ^{[1
]}

Niknam, Sharareh ^{[1
]}

Peltier, Heidi J. ^{[2
]}

Diao, Lixia ^{[3
]}

Giri, Uma ^{[4
]}

Komaki, Ritsuko ^{[5
]}

Calin, George A. ^{[6
]}

Gomez, Daniel R. ^{[5
]}

Chang, Joe Y. ^{[5
]}

Heymach, John Victor ^{[4
]}

Bader, Andreas G. ^{[2
]}

Welsh, James William ^{[5
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA

[2] Mirna Therapeut Inc, Austin, TX USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Computat Biol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2015年 / 4卷

关键词：

miR-34a; non-small-cell lung cancer; RAD51; radiation; STRAND BREAK REPAIR; HOMOLOGOUS RECOMBINATION; DNA-DAMAGE; CANCER-CELLS; ENHANCES RADIOSENSITIVITY; IONIZING-RADIATION; MAMMALIAN-CELLS; EXPRESSION; MICRORNA; P53;

D O I：

10.1038/mtna.2015.47

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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.

引用

页数：9

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