ADAR-Mediated RNA Editing Predicts Progression and Prognosis of Gastric Cancer

Chan, Tim; Qamra, Aditi; Tan, Kar Tong; Guo, Jing; Yang, Henry; Liu, Qi; Lin, Jaymie Siqi; Ng, Vanessa Hui En; Song, Yangyang; Hong, HuiQi; Tay, Su Ting; Liu, Yujing; Lee, Jeeyun; Rha, Sun Young; Zhu, Feng; So, Jimmy Bok Yan; Teh, Bin Tean; Yeoh, Khay Guan; Rozen, Steve; Tenen, Daniel G.; Tan, Patrick; Chen, Leilei

doi:10.1053/j.gastro.2016.06.043

Cited by 136 publications

(135 citation statements)

References 59 publications

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“…Although RNA editing was initially considered to be a rare event, limited specifically to coding exons within genes, high-throughput sequencing data have now revealed that it occurs more prevalently (23). In particular, A-to-I RNA editing mediated by ADARs is the most prominent form of RNA editing in humans, and various studies have recently demonstrated cancer-specific dysregulation of ADAR as well as subsequent site-specific RNA editing in several human cancers (9)(10)(11)24). More specifically, AZIN1 has been identified as one of the most frequently edited genes in HCC and esophageal cancers (9, 10).…”

Section: Discussionmentioning

confidence: 99%

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

Shigeyasu¹,

Okugawa²,

Toden³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

Shigeyasu¹,

Okugawa²,

Toden³

et al. 2018

JCI Insight

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“…AZIN1 ( 9 , 44 ) and NEIL1 ( 62 ) ) and impairs editing frequencies of ADAR2 substrates (e.g. COPA ( 46 ), GluA2 ( 63 ) and PODXL ( 32 ) ), respectively, are involved in cancer development and progression. As a bidirectional regulator of A-to-I editing, DHX9 reshapes the editing profiles, which may further contribute to the dysregulation in editing and confer malignant transformation of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…A bioinformatics pipeline adapted from a previously published method (31) was used to identify RNA editing events (32). For each sample, raw reads were mapped to the reference human genome (hg19) and a splicing junction database generated from transcript annotations derived from UCSC, RefSeq, Ensembl and GENCODE (v19) by using Burrows–Wheeler Aligner with default parameters (bwa mem algorithm, v0.7.15-r1140) (33).…”

Section: Methodsmentioning

confidence: 99%

Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer

Hong

Chan

et al. 2018

Nucleic Acids Research

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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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“…In gastric cancer, high ADAR1 levels are correlated with increased cell proliferation and metastasis. While one group reported earlier that the higher expression of ADAR1, together with lower ADAR2 levels, led to a “misedited” phenotype [142], another group suggested that ADAR1p150′s function was to promote the mTOR signaling pathway by phosphorylation [143], although whether editing also occurred was unclear. Further studies would be needed to determine how ADAR1p150 regulates phosphorylation of proteins like mTOR, and whether this pathway is generalizable to other cancers that are also associated with imbalances in ADAR1 levels.…”

Section: Regulation Of Adar1 Expressionmentioning

confidence: 99%

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

Song

Sakurai

Shiromoto

et al. 2016

Genes

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Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA (dsRNA). Among the three types of mammalian ADARs, ADAR1 has long been recognized as an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. Recent findings that ADAR1 is involved in the recognition of self versus non-self dsRNA provide potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Novel identifications of long noncoding RNA and retrotransposons as editing targets further expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners. Elucidating the disease-specific patterns of editing and/or ADAR1 expression may be useful in making diagnoses and prognoses. In this review, we relate the mechanisms of ADAR1′s actions to its pathological implications, and suggest possible mechanisms for the unexplained associations between ADAR1 and human diseases.

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ADAR-Mediated RNA Editing Predicts Progression and Prognosis of Gastric Cancer

Cited by 136 publications

References 59 publications

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

Bidirectional regulation of adenosine-to-inosine (A-to-I) RNA editing by DEAH box helicase 9 (DHX9) in cancer

Functions of the RNA Editing Enzyme ADAR1 and Their Relevance to Human Diseases

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