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Oncogene:动态m6A mRNA甲基化阐释了METTL3-m6A-CDCP1信号轴在化学致癌中的作用

2019-03-12 AlexYang MedSci原创

N6甲基腺苷(m6A)是哺乳动物mRNAs中最丰富的内在修饰。尽管在各种各样的生理过程中具有重要的功能,m6A在化学致癌中的作用仍旧未知。最近,有研究人员分析了化学致癌剂诱导细胞性状转化过程中动态m6A mRNA修饰过程情况,并鉴定了细胞转化相关的受调控的m6A位点。明显的是,研究人员在恶性转化细胞CDCP1致癌基因的mRNA 3′-UTR区域发现m6A增加。m6A甲基转移酶METTL3和脱甲基酶

N6甲基腺苷(m6A)是哺乳动物mRNAs中最丰富的内在修饰。尽管在各种各样的生理过程中具有重要的功能,m6A在化学致癌中的作用仍旧未知。

最近,有研究人员分析了化学致癌剂诱导细胞性状转化过程中动态m6A mRNA修饰过程情况,并鉴定了细胞转化相关的受调控的m6A位点。明显的是,研究人员在恶性转化细胞CDCP1致癌基因的mRNA 3′-UTR区域发现m6A增加。m6A甲基转移酶METTL3和脱甲基酶ALKBH5能够调节CDCP1 mRNA 3′-UTR区域的m6A修饰。METTL3和m6A识别因子YTHDF1能够倾向性的识别CPCP1 3′-UTR m6A残基和促进CDCP1的翻译。研究人员进一步展现了METTL3和CDCP1在膀胱癌患者样本中表达上调,并且METTL3和CDCP1的表达水平与膀胱癌的恶化状态相关。METTL3-m6A-CDCP1信号轴的抑制能够导致化学转化细胞和膀胱癌细胞生长和恶化的减少。更重要的是,体内和体外试验表明METTL3-m6A-CDCP1信号轴与化学致癌剂在促进上皮细胞致癌和膀胱癌肿瘤形成过程中具有协同作用。

最后,研究人员指出,他们的结果鉴定了化学诱导的恶性转化过程中动态的m6A修饰情况,并为METTL3-m6A-CDCP1在化学致癌过程中关键作用提供了新的认识。

原始出处:


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    2019-03-24 liuxiaona
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    2020-01-01 cy0324
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    2019-09-18 一闲
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    2020-01-14 kcb077
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    2019-03-14 jambiya
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    2019-03-14 zsyan

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