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.

Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients

“…Cells were used for experiments when they were around 60% to 70% confluent. Preferably, low passages (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were used. Irradiation assay Radiosensitivity assay.…”

“…miRs playing a role in radioresistance have been described, although experiments were done in cell line pairs and not in a larger panel of cell lines (18)(19)(20).…”

MicroRNA-409-3p Functions as a Tumor Suppressor in Human Lung Adenocarcinoma by Targeting c-Met

“…Xiang' et al showed that microRNA-98 could sensitize cisplatin-resistant human lung adenocarcinoma cells by up-regulation of HMGA2 [23]. Liu and his colleagues reported that microRNA-449a could enhance radiosensitivity in CL1-0 lung adenocarcinoma cells [24]. However, the roles of miR-409-3p in LAD progression remain unclear and need to be further elucidated.…”

Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

“…Studies have identified some novel miRNAs which are involved in the DNA repair pathway and regulate the DNA damage response to radiation (29)(30)(31). Yan et al (32) identified miR-101 as a molecule able to sensitize cancer cells to IR by targeting the 3'UTR of DNA-PKcs and ATM transcripts.…”