Oncogene:m6A甲基转移酶METT3能够促进膀胱癌的恶化

2019-01-31 AlexYang MedSci原创

N6-甲基腺苷(m6A)在真核生物信使RNAs(mRNAs)中是最丰富的修饰,并且在许多生物过程中都具有重要的作用。然而,它在膀胱癌(BCa)中的功能仍旧不清楚。最近,有研究人员发现类甲基转移酶-3(METTL3)(1种主要的RNA N6-腺苷酸甲基转移酶)在人类BCa中显著上调。METTL3的敲除能够剧烈的减少BCa细胞的增殖、入侵以及体外生存和体内的致瘤性。另一方面,METTL3的过表达能够显

N6-甲基腺苷(m6A)在真核生物信使RNAs(mRNAs)中是最丰富的修饰,并且在许多生物过程中都具有重要的作用。然而,它在膀胱癌(BCa)中的功能仍旧不清楚。

最近,有研究人员发现类甲基转移酶-3(METTL3)(1种主要的RNA N6-腺苷酸甲基转移酶)在人类BCa中显著上调。METTL3的敲除能够剧烈的减少BCa细胞的增殖、入侵以及体外生存和体内的致瘤性。另一方面,METTL3的过表达能够显著的促进BCa细胞的生长和入侵。通过转录组测序、m6A测序和m6A甲基化RNA免疫沉淀定量逆转录聚合酶链反应,研究人员首次表明METTL3调控的m6A修饰在BCa细胞中存在。AF4/FMR2家族成员4(AFF4)、2个关键的NF-κB途径调控因子(IKBKBRELA)以及MYC在进一步的研究中被鉴定为METTL3调控的m6A修饰的直接靶标。另外,研究人员还指出,除了NF-Κb,AFF4能够结合到MYC的启动子并促进其表达,表明了METTL3下游的新的多层次的调控网络。

最后,研究人员指出,他们的结果揭示了由METTL3调节的m6A修饰操纵的AFF4/NF-κB/MYC信号网络,并为BCa的发展机制提供了新的认识。

原始出处:

Maosheng Cheng, Lu Sheng, Qian Gao et al. The m6A methyltransferase METTL3 promotes bladder cancer progression via AFF4/NF-κB/MYC signaling network. Oncogene. 18 January 2019.

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    2019-04-07 一闲
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    2019-08-08 cy0324
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    2019-03-21 kcb077
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    2019-02-04 orangesking

    0

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    2019-02-02 zsyan

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