The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing
            <i>FAK</i>

Amin, Elianna; Liu, Yuan; Deng, Su; Tan, Kay See; Chudgar, Neel P.; Mayo, Marty W.; Sanchez‐Vega, Francisco; Adusumilli, Prasad S.; Schultz, Nikolaus; Jones, David R.

doi:10.1126/scisignal.aah3941

Cited by 57 publications

(50 citation statements)

References 60 publications

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“…For instance, A-to-I edited sites in the 3′UTR of cathepsin S mRNA, controls the mRNA stability allowing its interaction with HuR , a key mRNA stabilizing RNA binding protein [ 14 ]. Moreover, ADAR1 has been recently shown to interact and stabilize FAK mRNA through an edited site located in an intronic region, increasing the mobility and invasion capacities of lung adenocarcinoma cells [ 15 ]. This suggests that the A-to-I editing adds an additional level of complexity and plasticity in the function and regulation of the target, with unprecedented implications for diseases, such as cancer.…”

Section: Introductionmentioning

confidence: 99%

ADAR1-mediated RNA-editing of 3′UTRs in breast cancer

et al. 2018

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BackgroundWhole transcriptome RNA variant analyses have shown that adenosine deaminases acting on RNA (ADAR) enzymes modify a large proportion of cellular RNAs, contributing to transcriptome diversity and cancer evolution. Despite the advances in the understanding of ADAR function in breast cancer, ADAR RNA editing functional consequences are not fully addressed.ResultsWe characterized A to G(I) mRNA editing in 81 breast cell lines, showing increased editing at 3′UTR and exonic regions in breast cancer cells compared to immortalized non-malignant cell lines. In addition, tumors from the BRCA TCGA cohort show a 24% increase in editing over normal breast samples when looking at 571 well-characterized UTRs targeted by ADAR1. Basal-like subtype breast cancer patients with high level of ADAR1 mRNA expression shows a worse clinical outcome and increased editing in their 3′UTRs. Interestingly, editing was particularly increased in the 3′UTRs of ATM, GINS4 and POLH transcripts in tumors, which correlated with their mRNA expression. We confirmed the role of ADAR1 in this regulation using a shRNA in a breast cancer cell line (ZR-75-1).ConclusionsAltogether, these results revealed a significant association between the mRNA editing in genes related to cancer-relevant pathways and clinical outcomes, suggesting an important role of ADAR1 expression and function in breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s40659-018-0185-4) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

ADAR1-mediated RNA-editing of 3′UTRs in breast cancer

et al. 2018

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“…To our knowledge, very few studies have examined this question on the transcriptome-wide scale 65,66 . Previously, several studies demonstrated this regulatory role for a handful of editing sites through alteration of miRNA binding sequences or mRNA secondary structure or otherwise unknown mechanisms 6,20,[67][68][69][70][71][72] . Expanding on these previous studies, we incorporated tissue-rich data from GTEx and ADAR KD expression changes from five cell lines to computationally support associations of editing with mRNA abundance.…”

Section: Discussionmentioning

confidence: 99%

Differential RNA editing between epithelial and mesenchymal tumors impacts mRNA abundance in immune response pathways

Chan

Bahn

et al. 2020

Preprint

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Recent studies revealed global shifts in RNA editing, the modification of RNA sequences, across many cancers. Besides a few sites implicated in tumorigenesis or metastasis, most tumor-associated sites, predominantly in noncoding regions, have unknown function. Here, we characterize editing profiles between epithelial (E) and mesenchymal (M) phenotypes in seven cancer types, as epithelial-mesenchymal transition (EMT) is a key paradigm for metastasis. We observe distinct editing patterns between E and M tumors and EMT induction upon loss of ADAR enzymes in cultured cells. E-M differential sites are highly enriched in genes involved in immune and viral processes, some of which regulate mRNA abundance of their respective genes. We identify a novel mechanism in which ILF3 preferentially stabilizes edited transcripts. Among editing-dependent ILF3 targets is the transcript encoding PKR, a crucial player in immune response. Our study demonstrates the broad impact of RNA editing in cancer and relevance of editing to cancer-related immune pathways.

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“…Notably, knockdown of ADAR in lung adenocarcinoma cells with amplified ADAR leads to decreased migration and invasion [12]. Hence, pharmacological targeting of ADAR promise a potential therapeutic application for tumors with ADAR amplification.…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, ongoing studies have been elucidate role of ADAR in cancer development and progression. It has been shown that increased ADAR expression correlates with tumor recurrence in lung adenocarcinoma [12]. In addition, ADAR overexpression is connected with increased malignancy of breast, lung and liver cancer, and silencing of ADAR in breast cancer cells results in increased apoptosis.…”

mentioning

confidence: 99%

ADAR expression and copy number variation in patients with advanced gastric cancer

Behroozi

Shahbazi²,

Bakhtiarizadeh

et al. 2020

Preprint

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Background Gastric cancer (GC) is a world health problem and it is the third leading cause of cancer deaths worldwide. The current practice for prognosis assessment in GC is based on radiological and pathological criteria and they may not result in an accurate prognosis. The aim of this study is to evaluate expression and copy number variation of the ADAR gene in advanced GC and clarify its correlation with survival and histopathological characteristics. Methods Forty two patients with stage III and IV GC were included in this study. ADAR gene expression and copy number variation were measured by real-time PCR and Quantitative multiplex ﬂuorescent-PCR, respectively. Survival analysis performed based on the Kaplan–Meier method and Mantel–Cox test. Results ADAR mRNA was significantly overexpressed in the tumor tissues when compared to the adjacent normal tissues (p <0.01). Also, ADAR expression level in stage IV was higher than stage III. 40% of patients showed amplification in ADAR gene and there was a positive correlation between ADAR copy number and expression. Increased ADAR expression was clearly correlated with poorer survival outcomes and Mantel–Cox test showed statistically significant differences between low and high expression groups (p <0.0001). ADAR overexpression and amplification were significantly associated with metastasis, size and stage of tumor. Conclusions Together, our data indicate that amplification leads to over expression of ADAR and it could be used as a prognostic biomarker for disease progression, especially for the metastatic process in GC. Keywords Gastric cancer, ADAR gene, Overexpression, Amplification, Prognosis

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The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK

Cited by 57 publications

References 60 publications

ADAR1-mediated RNA-editing of 3′UTRs in breast cancer

ADAR1-mediated RNA-editing of 3′UTRs in breast cancer

Differential RNA editing between epithelial and mesenchymal tumors impacts mRNA abundance in immune response pathways

ADAR expression and copy number variation in patients with advanced gastric cancer

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