ArticleMolecular cancer2025
M6A-Methylated circRAPGEF5 drives lung adenocarcinoma progression and metastasis via IGF2BP2/NUP160-mediated autophagy suppression.
Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- SUCLG2 contributes to platinum resistance in lung adenocarcinoma through enhancing succinylation of GAC and glutamine metabolism.Apoptosis : an international journal on programmed cell death · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- mCancer science · 2026Article
- m6A-Driven Pexophagy Triggers Placental Ferroptosis to Impair Fetal Growth Upon Environmental Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Forsythiaside A inhibits progression and induces autophagy in lung adenocarcinoma: an integrated study combining network pharmacology and experimental validation.Scientific reports · 2026Article
- Identification of immune-related targets of N6-methyladenosine regulators in hepatocellular carcinoma via RNA-seq analysis.Translational cancer research · 2026Article
- Functional roles and mechanisms of circRNA-protein interactions in cancer progression and tumor immune regulation.Frontiers in immunology · 2026Review
- Emerging functions of m6A-modified circRNAs and their targeting strategies in lung cancer.Frontiers in cell and developmental biology · 2026Review
- METTL16 promotes PD-L1 expression and mediates immunosuppression in B-cell lymphomas via mAmerican journal of translational research · 2026Article
- The single-cell atlas of colorectal cancer reveals cellular heterogeneity and key molecular features of the tumor immune microenvironment.Cancer immunology, immunotherapy : CII · 2025Article
- Transcriptional regulation of nucleotide metabolism in medulloblastoma subtypes and prognostic implications analyzed by RNA-Seq.Journal of cancer research and clinical oncology · 2025Article
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10 authors.
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Abstract
backgroundLung adenocarcinoma (LUAD), the predominant histological subtype of non-small cell lung cancer, demonstrates critical regulatory involvement of RNA-binding proteins (RBPs) and circular RNAs (circRNAs) in tumorigenic processes. Emerging evidence highlights the circRNA-autophagy regulatory axis as a crucial modulator of cancer progression. This study systematically investigates the functional interplay within the RBP-circRNA-autophagy network in LUAD pathogenesis.
methodsEmploying RNA pull down, mass spectrometry and RNA immunoprecipitation facilitated the exploration of the circRAPGEF5 binding protein. M6A methylation RNA immunoprecipitation-PCR was utilized for m6A analysis. Immunofluorescence (IF) and fluorescence in situ hybridization (FISH) assays were conducted to ascertain the subcellular localization of target genes. Employing mRFP-GFP-LC3 fluorescent lentivirus labelling facilitated the monitoring of autophagy flow levels. Xenografts in mice were instrumental in affirming the role of circRAPGEF5.
resultsThrough comprehensive molecular profiling, we identified elevated circRAPGEF5 expression in LUAD cells, which significantly suppressed autophagic flux while promoting malignant phenotypes including enhanced proliferation, migration, and invasion. Mechanistic investigations revealed that circRAPGEF5 directly interacts with the KH3-4 functional domain of Insulin-like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2), an m6A reader protein. This interaction facilitated IGF2BP2-mediated stabilization of NUP160 mRNA, a nuclear pore complex component. Genetic ablation of NUP160 through RNA interference effectively restored autophagic activity, thereby attenuating the aggressive biological behaviors of LUAD cells. In vivo validation using xenograft models demonstrated that the circRAPGEF5/IGF2BP2/NUP160 signaling axis promotes tumor growth and metastatic dissemination through autophagy suppression.
conclusionOur findings reveal a novel epigenetic regulatory mechanism wherein m6A-modified circRAPGEF5 orchestrates autophagy inhibition via IGF2BP2-dependent stabilization of NUP160 transcripts, ultimately driving LUAD progression and metastasis. These results establish the circRAPGEF5/IGF2BP2/NUP160 axis as a potential therapeutic target for LUAD intervention.
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