Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway.
miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into A549 and H1299 cells, with or without co-treatment of γ-irradiation. Results showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy.
School of Radiation Medicine and Public Health, Soochow University, Suzhou, Jiangsu 215123, China.
Weiming
W
Duan
Yaxiang
Y
Xu
Yujin
Y
Dong
Lili
L
Cao
Jian
J
Tong
Xinwen
X
Zhou
D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
C569658:ARHGDIB protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; D011838:Radiation-Sensitizing Agents; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020830:rac1 GTP-Binding Protein
COX-2; LyGDI; Rac1; miR-34a; non-small cell lung cancer; radiosensitivity