Role of The circ-HIPK3, circ-PVT1, miR-25, and miR-149 in Response of Breast Cancer Cells to Ionizing Radiation

OBJECTIVE: Determining cellular radiosensitivity of breast cancer (BC) patients through molecular markers before radiation therapy (RT) allows accurate prediction of individual’s response to radiation. The aim of this study was therefore to investigate the potential role of epigenetic biomarkers in breast cancer cellular radiosensitivity. MATERIALS AND METHODS: In this experimental study, we treated two BC cell lines, MDA-MB 231 and MCF-7, with doses of 2, 4, and 8Gy of irradiation for 24 and 48 hours. Expression levels of circ-HIPK3, circ-PVT1, miR-25, and miR149 were quantified using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Significance of the observations was statistically verified using one-way ANOVA with a significance level of P<0.05. Annexin V-FITC/PI binding assay was utilized to measure cellular apoptosis. RESULTS: The rate of cell apoptosis was significantly higher in MCF-7 cells compared to MDA-MB-231 cells at doses of 4Gy and 8Gy (P=0.013 and P=0.004, respectively). RNA expression analysis showed that circ-HIPK3 was increased in the MDA-MB-231 cell line compared to the MCF-7 cell line after exposure to 8Gy for 48 hours. Expression of circ-PVT1 was found to be higher in MDA-MB-231 cells compared to MCF-7 cells after exposure to 8Gy for 24 hours, likewise after exposure to 4Gy and 8Gy for 48 hours. After exposing 8Gy, expression of miR-25 was increased in MDA-MB-231 cells compared to MCF-7 cells at 24 and 48 hours. After exposing 8Gy dose, expression of miR-149 was increased in MCF-7 cells compared to MDA-MB-231 cells at 24 and 48 hours. CONCLUSION: circ-HIPK3, circ-PVT1, and miR-25 played crucial roles in the mechanisms of radioresistance in breast cancer. Additionally, miR-149 was involved in regulating cellular radiosensitivity. Therefore, these factors provided predictive information about a tumor’s radiosensitivity or its response to treatment, which could be valuable in personalizing radiation dosage.