Evidence map›Paper›PMID 40629330›Full record

ArticleMolecular cancer2025

M6A-Methylated circRAPGEF5 drives lung adenocarcinoma progression and metastasis via IGF2BP2/NUP160-mediated autophagy suppression.

Liqun Ling, Tianqi Hu, Chenkang Zhou, Yingjie Dai, Lijuan Hu, Yuxin Chen, Zhaoting Hu, Kate Huang, Jie Chen, Yumin Wang

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
  2. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
  3. Review
  4. mCancer science · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Review
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  10. Article
  11. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Liqun LingDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Tianqi HuDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Chenkang ZhouCixi Biomedical Research Institute, Wenzhou Medical University, Wenzhou, 325000, China.
Yingjie DaiDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Lijuan HuDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Yuxin ChenDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Zhaoting HuDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China.
Kate HuangDepartment of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Jie ChenDepartment of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. chenjie991300@163.com.
Yumin WangDepartment of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, 325000, China. wym0577@163.com.

Funding

the Discipline Cluster of Oncology, Wenzhou Medical University, China NO.z1-2023006the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province 2022E10022the Zhejiang Provincial Health Planning Commission 2023KY902the Zhejiang Provincial Natural Science Foundation ZCLY24H2001the Zhejiang Provincial Research Center for Cancer Intelligent Diagnosis and Molecular Technology JBZX-202003
6 · The paper itself

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.

Indexed as

Adenocarcinoma of LungAutophagyGuanine Nucleotide Exchange FactorsLung NeoplasmsNuclear Pore Complex ProteinsRNA-Binding ProteinsRNA, CircularAdenosineAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMethylationAdenosineGuanine Nucleotide Exchange FactorsIGF2BP2 protein, humanN-methyladenosineNuclear Pore Complex ProteinsRNA-Binding ProteinsRNA, Circular

Identifiers

PMID40629330
PMCPMC12236038

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.