Role of ADAR1 on transcriptional output in cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE275573 | GEO | 2025/08/14
REPOSITORIES: GEO
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Project description:The loss of ADAR1 significantly reduced ribosome production, decreased tumor translational efficiency, and impaired the translation of oncogenic pathways. And NOP14 significantly upregulated ribosome production and tumor translational efficiency.
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Project description:The loss of ADAR1 significantly reduced ribosome production, decreased tumor translational efficiency, and impaired the translation of oncogenic pathways.
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Project description:Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a widespread modification in mammals. Cumulative evidence has suggested the altered A-to-I editing profile in prostate cancer (PCa), but the underlying mechanism remains unclear. Here, we discover enhancer of zeste homologue 2 (EZH2) as a novel ADAR interactor and editing regulator in PCa. Through competing with Interleukin Enhancer Binding Factor 2 (ILF2) for ADAR1 binding, EZH2 reshapes the substrate selectivity of ADAR1 and thus exhibits a bidirectional role in editing regulation. Moreover, EZH2 depletion induces the translational repression of Transportin-1 (TRN1), which further results in the accumulation of cytoplasmic ADAR1 to protect many oncogenic transcripts from degradation. Consistently, depletion of ADAR1 dramatically enhances the sensitivity of PCa cells and tumors to EZH2 selective degraders. Collectively, our study highlights the significance of EZH2-ADAR1 cascade in governing RNA editing and mRNA stability, which may provide novel perspectives for the advancement of EZH2-targeting cancer therapies.
2025-11-15 | GSE225951 | GEO
Project description:This study aims to delineate the role of ADAR1 in human cells beyond its canonical function as an interferon-stimulated gene (ISG). Human monocyte-derived macrophages were subjected to RNA interference targeting either pan-ADAR1 (both isoforms) or the p150 isoform specifically. Quantitative proteomic analyses were performed using state-of-the-art isobaric tandem mass tag (TMT) labeling coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Strikingly, silencing of ADAR1 significantly impacted prototypical macrophage functions, including endocytosis, cholesterol metabolism, and lysosomal processing, without concurrent induction of pro-inflammatory or ISG responses. Pan-ADAR1 silencing resulted in upregulation of proteins involved in lysosomal function and cholesterol processing, whereas selective depletion of ADAR1-p150 led to downregulation of pathways associated with phagocytosis and endocytosis. Moreover, loss of pan-ADAR1 caused a marked downregulation of cell-cycle and p53 signaling pathways, suggesting a potential role for the ADAR1-p110 isoform in regulating cell proliferation. Collectively, these data define previously unappreciated proteomic alterations driven by ADAR1 that influence fundamental macrophage functions beyond its established ISG role.
2026-02-13 | PXD073582 | Pride
Project description:Aberrant RNA-editing was observed in several human tumors, but its significance is mostly unknown. Here we show that ADAR1, a ubiquitous RNA-editing enzyme, is commonly lost in metastatic melanoma cells and specimens. Experimental ADAR1 silencing significantly alters melanoma cell morphology, facilitates proliferation and cell-cycle, and increases the tumorigenicity in-vivo. A series of ADAR1 truncation mutants establishes a novel RNA-editing-independent role for ADAR1 in controlling the nuclear and cytoplasmic processing steps of miRNA biogenesis. Altered expression of ADAR1-controled miRNAs accounts for the observed phenotype. We show that the oncogenic miR-17-5p endogenously regulates ADAR1 expression and that its genomic sequence is frequently amplified in melanoma to overexpress the mature miR-17-5p form. ADAR1 and miR-17-5p are ubiquitously expressed, suggesting the generality of this mechanism. Melanoma cell line expressing low ADAR1 levels (ADAR1-Knockdown) using shRNA technique were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to examine the alterations in the genes and microRNA expression profile in the manipulated cell system, due to ADAR1 possible involvement cancer development. To that end, we selected ADAR1-knockdown (ADAR1-KD) cells that demonstrated an enhanced aggressive phenotype both in vivo and in vitro as compared to the control cells (Control).
2012-08-31 | E-GEOD-31963 | biostudies-arrayexpress
Project description:Role of ADAR1 on transcriptional output in cancer cells
| PRJNA1152573 | ENA
Project description:Role of ADAR1 on transcriptional output in cancer cells
| PRJNA1151690 | ENA
Project description:Aberrant RNA-editing was observed in several human tumors, but its significance is mostly unknown. Here we show that ADAR1, a ubiquitous RNA-editing enzyme, is commonly lost in metastatic melanoma cells and specimens. Experimental ADAR1 silencing significantly alters melanoma cell morphology, facilitates proliferation and cell-cycle, and increases the tumorigenicity in-vivo. A series of ADAR1 truncation mutants establishes a novel RNA-editing-independent role for ADAR1 in controlling the nuclear and cytoplasmic processing steps of miRNA biogenesis. Altered expression of ADAR1-controled miRNAs accounts for the observed phenotype. We show that the oncogenic miR-17-5p endogenously regulates ADAR1 expression and that its genomic sequence is frequently amplified in melanoma to overexpress the mature miR-17-5p form. ADAR1 and miR-17-5p are ubiquitously expressed, suggesting the generality of this mechanism.
2012-08-31 | GSE31963 | GEO
Project description:Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a key post-transcriptional modification that regulates RNA splicing, stability, and translation. Dysregulation of ADAR activity caused by mutations in ADAR1 leads to Aicardi-Goutières syndrome (AGS), an autoimmune disorder characterized by aberrant activation of Melanoma differentiation-associated protein 5 (MDA5) by self RNA and excessive type I interferon production. Despite its biological and clinical relevance, the regulation of ADAR1 activity remains incompletely understood. Here, we show that ADAR1 protein levels and RNA editing activity in mammalian cells critically depend on the cofactor inositol hexakisphosphate (IP6). Using Inositol-pentakisphosphate 2-kinase (IPPK)-knockout cells, next-generation sequencing (NGS), and a cell-permeable IP6 prodrug (Pro-IP6), we demonstrate that IP6 depletion drastically reduces global RNA editing, while supplementation with Pro-IP6 restores and even enhances editing levels. In vitro ADAR1 translation and RNA editing assays revealed that IP6 contributes to the folding and full catalytic activity of ADAR1, and that inositol pentakisphosphate (1,3,4,5,6-IP5) can partially substitute IP6 as a cofactor. Molecular dynamics simulations and biochemical analyses identified the C6-phosphate of IP6 as a critical determinant of ADAR1 catalytic efficiency, functioning within a hydrogen-bonding network that indirectly governs Zn²⁺-ion positioning through interactions with key residues, including K1039 and N907. Notably, the AGS-associated N907S mutation impairs RNA editing, by altering IP6 coordination and introducing more dynamic situation in the hydrogen-bonding network of IP6 and Zn²⁺-ion. Together, these findings identify IP6 as an essential cofactor and regulator of ADAR1 activity. Through a network of interactions and the availability of IP6, this may represent a new strategy for therapeutically controlling RNA editing in the disease.
2026-01-20 | GSE316528 | GEO
Project description:The purpose of this study was to examine the role of MAVS, ZBP1 and RIPK3 in the phenotype that develops when ADAR1 activity is impaired, in particular when the Za domain of ADAR1 is mutated. Mice homozygous for a Za domain-mutant allele of Adar1 (Adar1mZa/mZa mice) and mice carrying one mZa and one null Adar1 allele (Adar1-/mZa mice) were compared with control mice that were either wild type or heterozygous for the Adar1 mZa allele (Adar1wt/mZa mice). The effects of MAVS deficiency, RIPK3 deficiency, ZBP1 deficiency or ZBP1 Za domain mutations were assessed by analysing compound mutant mice. Given the early postnatal lethal phenotype that develops in Adar1-/mZa mice, comparisons were made in RNA isolated from lung tissue from newborn mice of each genotype (5 mice per genotype). As Adar1-/mZa mice additionally lacking Mavs or Zbp1 are viable, adult mice (15-20 weeks of age) were also used for several compound mutations as donors of lung tissue.
2022-06-09 | E-MTAB-11540 | biostudies-arrayexpress