Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer.
Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer.
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DOI：
10.1093/nar/gky396
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发表时间：
2018-09-06
影响因子：
14.9
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Hong H;An O;Chan THM;Ng VHE;Kwok HS;Lin JS;Qi L;Han J;Tay DJT;Tang SJ;Yang H;Song Y;Bellido Molias F;Tenen DG;Chen L
腺苷-肌苷（A-to-I） RNA编辑需要通过作用于RNA的腺苷脱氨酶（ADARs）将腺苷酶解为肌苷。失调的a -to- 1编辑与包括癌症在内的多种疾病有关。然而，控制a -to- i编辑及其生理病理意义的确切因素仍然是一个长期存在的问题。在此，我们揭示了DEAH盒解旋酶9 (DHX9)，至少部分依赖于其解旋酶活性，在癌细胞中作为a -to- i编辑的双向调节剂发挥作用。有趣的是，ADAR底物特异性决定了DHX9对编辑的相反作用，因为DHX9沉默优先抑制adar1特异性底物的编辑，而增强adar2特异性底物的编辑。对来自癌症基因组图谱（TCGA）的11种癌症类型的分析揭示了DHX9在肿瘤中的显著过表达。此外，致瘤性研究表明，DHX9在癌症发展中具有解旋酶依赖性的致癌作用。综上所述，DHX9在a -to- i编辑中构成了一种双向调控模式，这在一定程度上导致了癌症中编辑体谱的失调。
Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on RNA (ADARs). Dysregulated A-to-I editing has been implicated in various diseases, including cancers. However, the precise factors governing the A-to-I editing and their physiopathological implications remain as a long-standing question. Herein, we unravel that DEAH box helicase 9 (DHX9), at least partially dependent of its helicase activity, functions as a bidirectional regulator of A-to-I editing in cancer cells. Intriguingly, the ADAR substrate specificity determines the opposing effects of DHX9 on editing as DHX9 silencing preferentially represses editing of ADAR1-specific substrates, whereas augments ADAR2-specific substrate editing. Analysis of 11 cancer types from The Cancer Genome Atlas (TCGA) reveals a striking overexpression of DHX9 in tumors. Further, tumorigenicity studies demonstrate a helicase-dependent oncogenic role of DHX9 in cancer development. In sum, DHX9 constitutes a bidirectional regulatory mode in A-to-I editing, which is in part responsible for the dysregulated editome profile in cancer.
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影响因子：
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