Radiosensitization Following Valproic Acid and Gamma Rays in Anaplastic Thyroid Cancer Cells Increases the Expression of hsa-miR-26a-5p

Abstract

Background. Anaplastic thyroid cancer (ATC) is a rare lethal human malignancy with a poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available anticonvulsant and histone deacetylase inhibitor with a well-documented side effect profile. Furthermore, VA radiosensitizes various cancer cells, including thyroid cancer. MicroRNAs (miRs) are deregulated in several cancers and may modulate radiation response. Therefore, the aim of this study was to analyze the effect of VA combined with gamma radiation in radioresistant ATC cells at the expression level of miRs. Methods. ATC cells (8505c and KTC-2) were VA-treated and gamma-irradiated (2 Gy). The expression profile of miRs in 8505c was evaluated by microarray analysis 4 h after irradiation. Selected miRs were validated by RT-qPCR in both types of ATC cells. Results. We observed that after combined VA and gamma irradiation treatment, 8505c cells showed 109 differentially expressed miRs as compared to irradiated cells alone. These miRs exhibited a radiosensitization profile highlighted by upregulation of hsamiR-26a-5p, which is usually downregulated in aggressive thyroid cancers. Moreover, hsa-miR-27a-3p and hsa-miR-486–5p, which are often deregulated in thyroid neoplasms, were downregulated after irradiation and VA treatment, respectively. The expression level of these three miRs was validated in 8505c and KTC-2 cells after treatments. Conclusion. The regulated miRs by VA and gamma irradiation reveal a novel miR expression profile with potential to be further studied in the radio-induced response and radiosensitization of ATC cells.