Zhou Shun, Bai Zhou-Lan, Xia Di, Zhao Zhi-Jun, Zhao Ren, Wang Yan-Yang, Zhe Hong
Graduated School, Ningxia Medical University, Yinchuan, Ningxia, China.
Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Mol Carcinog. 2018 May;57(5):590-597. doi: 10.1002/mc.22782. Epub 2018 Feb 1.
The role of N -methyladenosine (m A) demethylase fat mass and obesity-associated protein (FTO) in the regulation of chemo-radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of β-catenin by reducing m A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity. Clinically, the prognostic value of FTO for overall survival is found to be dependent on β-catenin expression in human CSCC samples. Taken together, these findings uncover a critical function for FTO and its substrate m A in the regulation of chemo-radiotherapy resistance, which may bear potential clinical implications for CSCC treatment.
N-甲基腺苷（m⁶A）去甲基化酶脂肪量与肥胖相关蛋白（FTO）在化疗放疗抗性调节中的作用在很大程度上仍不清楚。在此，我们表明，与各自相邻的正常组织相比，宫颈鳞状细胞癌（CSCC）组织中FTO的mRNA水平升高。FTO通过降低其mRNA转录本中的m⁶A水平来调节β-连环蛋白的表达，从而在体外和体内增强化疗放疗抗性，进而增加切除修复交叉互补组1（ERCC1）的活性。临床上，发现FTO对总生存期的预后价值取决于人类CSCC样本中β-连环蛋白的表达。综上所述，这些发现揭示了FTO及其底物m⁶A在化疗放疗抗性调节中的关键作用，这可能对CSCC治疗具有潜在的临床意义。
