Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis

@article{Anadn2015GeneAO,
  title={Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis},
  author={Carolina Plou Anad{\'o}n and Sonia Guil and Laia Sim{\'o}-Riudalbas and C{\'a}tia Moutinho and Fernando Seti{\'e}n and Anna Mart{\'i}nez-Card{\'u}s and Sebasti{\'a}n Moran and Alberto Villanueva and M{\'o}nica Calaf and August Vidal and Pedro A. Lazo and Ilse Zondervan and Suvi Savola and Takashi Kohno and Jun Yokota and Lluís Ribas de Pouplana and Manel Esteller},
  journal={Oncogene},
  year={2015},
  volume={35},
  pages={4407 - 4413},
  url={https://api.semanticscholar.org/CorpusID:9983952}
}
It is shown that the adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein.
View on Nature
nature.com
83 Citations
Highly Influential Citations
2
Background Citations
29
Methods Citations
2
Results Citations
3

83 Citations

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

It is demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC and its RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

Global Transcriptome Analysis of RNA Abundance Regulation by ADAR in Lung Adenocarcinoma

The RNA editing enzyme ADAR modulated by the rs1127317 genetic variant diminishes EGFR-TKIs efficiency in advanced lung adenocarcinoma.

Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma

It is shown that expression of ADar1 correlates with poor patient outcomes, and that ADAR1-mediated editing of GLI1 is a mechanism relevant in the context of multiple myeloma progression and drug resistance, andADAR1 knockdown reduces regeneration of high-risk MM in serially transplantable patient-derived xenografts.

ADAR1 Editing and its Role in Cancer

The regulatory mechanisms of ADar1 during tumorigenesis through aberrant editing of specific substrates are discussed and it is hypothesized that elevated ADAR1 levels play a role in suppressing an innate immunity response in cancer cells.

Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries

A bioluminescent reporter system that facilitates rapid and accurate determination of endogenous ADAR1 editing activity is described, based on the highly sensitive and quantitative Nanoluciferase that is conditionally expressed upon reporter-transcript editing.

Aberrant overexpression of ADAR1 promotes gastric cancer progression by activating mTOR/p70S6K signaling

It is concluded that ADAR1 contributes to gastric cancer development and progression via activating mTOR/p70S6K/S6 ribosomal protein signaling axis and may represent a new novel therapeutic opportunities.

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

It is found that the RNA-editing protein ADAR acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK), suggesting a potential therapeutic application for LUAD that has a high abundance of ADAR.

Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis.

It is identified that the MM transcriptome is aberrantly hyperedited because of the overexpression of ADAR1, and functional assays established ADAR2 to be oncogenic, driving cellular growth and proliferation in an editing-dependent manner and NEIL1 as an essential and a ubiquitously edited ADar1 target in MM.

ADAR1 Prevents R-loop Accumulation-Driven ATR Pathway Activation in Ovarian Cancer

It is demonstrated that ADAR1 was highly expressed in ovarian cancer tissues and negatively correlated with progression free survival of ovarian cancer patients and a potential target for ovarian cancer therapy.
...

24 References

Adenosine-to-inosine RNA editing mediated by ADARs in esophageal squamous cell carcinoma.

It is revealed that altered gene-specific A-to-I editing events mediated by ADAR1 drive the development of ESCC, with potential implications in diagnosis, prognosis, and treatment of this disease.

Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma

A better understanding of human hepatocellular carcinoma (HCC) pathogenesis at the molecular level will facilitate the discovery of tumor-initiating events. Transcriptome sequencing revealed that…

A disrupted RNA editing balance mediated by ADARs (Adenosine DeAminases that act on RNA) in human hepatocellular carcinoma

In vitro and in vivo functional assays prove that ADAR1 functions as an oncogene while ADAR2 has tumour suppressive ability in HCC, highlighting the fact that the differentially expressed ADARs in tumours has great prognostic value and diagnostic potential for HCC.

ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia

The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that…

The emerging role of RNA and DNA editing in cancer.

Targeting miR-381-NEFL axis sensitizes glioblastoma cells to temozolomide by regulating stemness factors and multidrug resistance factors

The miR-381-NEFL axis is important for TMZ resistance in GBM and may potentially serve as a novel therapeutic target for glioma.

Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells.

The results indicate that the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis and EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.

Differential Pathogenesis of Lung Adenocarcinoma Subtypes Involving Sequence Mutations, Copy Number, Chromosomal Instability, and Methylation

The lung adenocarcinoma intrinsic molecular subtypes co-occur with grossly distinct genomic alterations and with patient therapy response and nominate patient subgroups for future evaluation of treatment response.

Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene

A lentiviral vector expressing a cell suicide gene, the herpes simplex virus thymidine kinase (HSV-TK) gene, under the regulation of a miRNA, miR-128, that was found to be enriched in non-tumor brain tissue yet down-regulated in glioblastomas was designed.

Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

An unbiased genome-wide approach was used to identify 239 sites (in 207 target genes), with stringent criteria for editing, which included 10 of the 13 known edited genes and suggested that many more human genes may be edited at lower frequencies.