title: MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells.
abstract: Lung cancer is the leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for treating lung cancer, but it often fails because of the relative non-susceptibility of lung cancer cells to radiation. MicroRNAs (miRNAs) have been reported to modulate the radiosensitivity of lung cancer cells and have the potential to improve the efficacy of radiotherapy. The purpose of this study was to identify a miRNA that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5) with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips. Twenty-six miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation.
authors.affiliation: Graduate Institute of Physiology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Jyun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Lin
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Chen
authors.forename: En-Ching
authors.initials: EC
authors.lastname: Luo
authors.forename: Yuh-Ping
authors.initials: YP
authors.lastname: Sher
authors.forename: Mong-Hsun
authors.initials: MH
authors.lastname: Tsai
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Chuang
authors.forename: Liang-Chuan
authors.initials: LC
authors.lastname: Lai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000528:radiation effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics* / Q000528:radiation effects
chemical_list: C544530:MIRN449 microRNA, human; D035683:MicroRNAs