Abdollahi Elahe, Mozdarani Hossein
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Email:
Cell J. 2023 Oct 1;25(10):688-695. doi: 10.22074/cellj.2023.1995943.1255.
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.
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 miR- 149 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.
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.
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.
在放射治疗（RT）前通过分子标志物确定乳腺癌（BC）患者的细胞放射敏感性，有助于准确预测个体对放疗的反应。因此，本研究旨在探讨表观遗传生物标志物在乳腺癌细胞放射敏感性中的潜在作用。
在本实验研究中，我们用2、4和8Gy剂量的辐射分别处理两种乳腺癌细胞系MDA-MB 231和MCF-7，处理时间为24小时和48小时。使用定量逆转录聚合酶链反应（qRT-PCR）对circ-HIPK3、circ-PVT1、miR-25和miR-149的表达水平进行定量分析。采用单因素方差分析对观察结果的显著性进行统计学验证，显著性水平为P<0.05。利用膜联蛋白V-FITC/PI结合试验检测细胞凋亡情况。
在4Gy和8Gy剂量下，MCF-7细胞的凋亡率显著高于MDA-MB-231细胞（分别为P=0.013和P=0.004）。RNA表达分析表明，在8Gy照射48小时后，MDA-MB-231细胞系中的circ-HIPK3表达量高于MCF-7细胞系。在8Gy照射24小时后，MDA-MB-231细胞中circ-PVT1的表达高于MCF-7细胞，同样，在4Gy和8Gy照射48小时后也是如此。在8Gy照射后，MDA-MB-231细胞中miR-25在24小时和48小时的表达量均高于MCF-7细胞。在8Gy剂量照射后，MCF-7细胞中miR-149在24小时和48小时的表达量高于MDA-MB-231细胞。
circ-HIPK3、circ-PVT1和miR-25在乳腺癌的放射抵抗机制中起关键作用。此外，miR-149参与调节细胞放射敏感性。因此，这些因素为肿瘤的放射敏感性或其对治疗的反应提供了预测信息，这对于个性化放疗剂量具有重要价值。
