FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting -catenin through mRNA demethylation
FTO regulates the chemo-radiotherapy resistance of cervical squamous cell carcinoma (CSCC) by targeting -catenin through mRNA demethylation
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FTO通过mRNA去甲基化靶向-catenin调节宫颈鳞状细胞癌（CSCC）的放化疗耐药
DOI：
10.1002/mc.22782
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发表时间：
2018-05-01
影响因子：
4.6
通讯作者：
Zhe, Hong
中科院分区：
文献类型：
--
作者：
Zhou, Shun;Bai, Zhou-Lan;Zhe, Hong
N-6-甲基腺苷（m（6）A）脱甲基酶、脂肪量和肥胖相关蛋白（FTO）在调控放化疗抵抗中的作用仍不清楚。在这里，我们表明，FTO的mRNA水平升高，在宫颈鳞状细胞癌（CSCC）组织相比，相应的相邻正常组织。FTO通过降低m（6）A mRNA转录水平调节β-catenin的表达，进而增加切除修复交叉互补组1（ERCC 1）活性，增强体外和体内的放化疗抗性。临床上，FTO对总生存期的预后价值被发现依赖于人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m（6）A在调节放化疗抗性中的关键功能，这可能对CSCC治疗具有潜在的临床意义。
The role of N-6-methyladenosine (m(6)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 -catenin by reducing m(6)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 -catenin expression in human CSCC samples. Taken together, these findings uncover a critical function for FTO and its substrate m(6)A in the regulation of chemo-radiotherapy resistance, which may bear potential clinical implications for CSCC treatment.