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.
Highlights
Lung cancer ranks first among cancer-related causes of death during the past few decades in Taiwan, and the mortality of lung cancer is increasing annually
CL1-0 cells are more radioresistant than CL1-5 CL1-0 and CL1-5 were regarded as a good model for metastasis-associated studies, because CL1-5 cells are more aggressive than non-metastatic CL1-0 cells
We demonstrated that two lung adenocarcinoma cell lines with an isogenic background, CL1-0 and CL1-5, displayed different radioresponses, and identified miR-449a as a regulator of their radiosensitivity
Summary
Lung cancer ranks first among cancer-related causes of death during the past few decades in Taiwan, and the mortality of lung cancer is increasing annually. Lung cancer can be classified into two major groups: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter group is further divided into subtypes of squamous cell carcinoma, large cell carcinoma and adenocarcinoma. Among these three, adenocarcinoma is the most common subtype and has a high mortality rate. One of the main causes of failure in radiotherapy is radioresistance [2]. A better understanding of how radioresistance is developed at the molecular level is needed to develop effective radiotherapy strategies in the future
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