Liu Sha, Pan Xiaofen, Yang Qin, Wen Lu, Jiang Yao, Zhao Yingchao, Li Guiling
Cancer Center, Wuhan Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430023, P.R. China.
Oncol Rep. 2015 Jun;33(6):2853-62. doi: 10.3892/or.2015.3929. Epub 2015 Apr 27.
Evidence has demonstrated that microRNAs (miRNAs) are important in the regulation of cellular radiosensitivity of various types of human cancer. The aim of this study was to examine the role of miR-18a in regulating the radiosensitivity of cervical cancer, in order to understand the underlying mechanism and to assess the potential of miR-18a as a biomarker for predicting radiosensitivity. The expression of miR-18a was investigated in 48 cervical cancer patients. The results revealed that miR-18a expression was significantly higher in radiosensitive patients than in radioresistant patients by RT-qPCR (P<0.05). Transient transfection experiments showed that miR-18a was upregulated by the miR-18a mimic and downregulated by the miR-18a inhibitor in the SiHa and HeLa cells. Without irradiation treatment, a similar growth was observed in the cells with or without transfection of miR-18a. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Hoechst staining assays showed that miR-18a had no effect on the proliferation and apoptosis of cervical cancer cells after transfection. However, the upregulation of miR-18a suppressed the level of ataxia-telangiectasia mutated and attenuated DNA double-strand break repair after irradiation, which re-sensitized the cervical cancer cells to radiotherapy by promoting apoptosis. Taken together, these results demonstrated that miR-18a is a potential molecule predictor of radiosensitivity in cervical cancer patients and played an important role in the response to radiotherapy.
有证据表明，微小RNA（miRNA）在调节各类人类癌症的细胞放射敏感性方面具有重要作用。本研究旨在探讨miR-18a在调节宫颈癌放射敏感性中的作用，以了解其潜在机制，并评估miR-18a作为预测放射敏感性生物标志物的潜力。对48例宫颈癌患者的miR-18a表达进行了研究。结果显示，通过RT-qPCR检测，放射敏感患者的miR-18a表达显著高于放射抵抗患者（P<0.05）。瞬时转染实验表明，在SiHa和HeLa细胞中，miR-18a模拟物可上调miR-18a表达，而miR-18a抑制剂则可下调其表达。在未进行辐照处理的情况下，转染或未转染miR-18a的细胞生长情况相似。3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）和Hoechst染色分析表明，转染后miR-18a对宫颈癌细胞的增殖和凋亡无影响。然而，miR-18a的上调抑制了共济失调毛细血管扩张症突变蛋白的水平，并减弱了辐照后DNA双链断裂的修复，通过促进凋亡使宫颈癌细胞对放疗重新敏感。综上所述，这些结果表明miR-18a是宫颈癌患者放射敏感性的潜在分子预测指标，在放疗反应中发挥重要作用。
