MicroRNA Dysregulation in Human Thyroid Cells Following Exposure to Ionizing Radiation

Abstract

Ionizing radiation is a well-known mutagen and a risk factor for thyroid cancer. MicroRNAs (miRNAs) play an important role in the regulation of gene expression on post-transcriptional level and are dysregulated in thyroid cancer. The goal of this study was to investigate the effects of acute exposure to 1 and 10 Gy of γ-irradiation on miRNA expression in normal human thyroid cells. Expression of 319 miRNAs was studied in primary cultures of normal human thyroid cells 4 and 24 hours postirradiation using a miRNA expression array with further confirmation of miRNAs expression by reverse transcription-polymerase chain reaction. We identified 30 miRNAs that were unregulated or downregulated more than twofold after irradiation as compared to nonirradiated thyroid cells, with no significant difference found between 1 and 10 Gy of radiation. Four distinct patterns of miRNA expression change were observed: miRNAs downregulated at 4 hours and returned to normal levels at 24 hours, miRNAs upregulated at 4 hours and returned to normal levels at 24 hours, and miRNAs either upregulated or downregulated at both time points. No dysregulation of miRNAs known to occur in thyroid cancer was observed. Acute exposure of thyroid cells to γ-radiation results in several specific patterns of miRNA response. It appears that alteration in miRNA expression seen 4-24 hours after irradiation has no direct association with carcinogenesis. However, it is likely to affect other cell functions, such as DNA repair.