Bidirectional Regulation of Adenosine-to-inosine (A-to-I) RNA Editing by DEAH Box Helicase 9 (DHX9) in Cancer

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2018 May 26

PMID 29796672

Citations 33

Authors

Huiqi Hong

Omer An

Tim H M Chan

Vanessa H E Ng

Hui Si Kwok

Jaymie S Lin

Lihua Qi

Jian Han

Daryl J T Tay

Sze Jing Tang

Henry Yang

Yangyang Song

Fernando Bellido Molias

Daniel G Tenen

Leilei Chen

Affiliations

Soon will be listed here.

Abstract

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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