Evidence map›Paper›PMID 40100806›Full record

ArticlePLoS genetics2025

MEOX1-mediated transcriptional regulation of circABHD3 exacerbates hepatic fibrosis through promoting m6A/YTHDF2-dependent YPEL3 mRNA decay to activate β-catenin signaling.

Limin Chen, Hui Yang, Juan Wang, Haoye Zhang, Kangkang Fu, Yu Yan, Zhenguo Liu

Abstract read
In one paragraph

Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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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

7 authors.

Limin ChenDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Hui YangDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Juan WangDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Haoye ZhangDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Kangkang FuDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Yu YanDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Zhenguo LiuDepartment of Infectious Disease, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.ORCID https://orcid.org/0000-0003-2696-6535

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHepatic fibrosis may progress to liver cirrhosis and eventually cause death. Epithelial-mesenchymal transition (EMT) of hepatocytes plays critical roles in hepatic fibrosis. Exploring the mechanisms underlying EMT is crucial for a better understanding of hepatic fibrosis pathogenesis.

methodsHepatocyte EMT wad induced with TGF-β1 and evaluated by Western blotting and immunofluorescence staining. Methylated RNA immunoprecipitation (MeRIP) was applied to assess N6-methyladenosine (m6A) modification. RIP and RNA pull-down assays were performed to analyze the interaction between circABHD3, YTHDF2 and YPEL3 mRNA. MEOX1-mediated transcription of ABHD3 was examined by luciferase and chromatin immunoprecipitation (ChIP). Mice were intraperitoneally injected with CCl4 or treated with bile duct ligation (BDL) surgery for hepatic fibrosis induction. Liver injury and collagen deposition were examined with hematoxylin and eosin (HE), Masson, and Sirius Red staining. Alanine transaminase (ALT), aspartate transaminase (AST) and hydroxyproline (HYP) were examined using ELISA.

resultsCircABHD3 was upregulated in in vitro and in vivo models of hepatic fibrosis and patients. Knockdown of circABHD3 inhibited TGF-β1-induced expression of fibrosis markers, EMT and mitochondrial impairment in hepatocytes. MEOX1 could directly bind to the promoter of ABHD3 to facilitate its transcription and subsequent circABHD3 generation. Knockdown of MEOX1 suppressed TGF-β1-induced EMT and mitochondrial impairment through suppression of circABHD3. CircABHD3 destabilized YPEL3 mRNA via promoting YTHDF2-dependent recognition of m6A-modified YPEL3 mRNA to trigger β-catenin signaling activation. Furthermore, circABHD3 silencing-mediated inhibition of EMT and mitochondrial impairment was counteracted by YPEL3 knockdown and activation of β-catenin signaling. Depletion of circABHD3 significantly reduced EMT, mitochondrial impairment and hepatic fibrosis via promoting YPEL3 expression and suppressing β-catenin signaling in vivo.

conclusionMEOX1-mediated generation of circABHD3 promotes EMT and mitochondrial impairment by enhancing YTHDF2-mediated degradation of YPEL3 mRNA and activating downstream β-catenin signaling, thus exacerbating hepatic fibrosis.

Indexed as

Homeodomain ProteinsLiver CirrhosisTranscription FactorsAnimalsCell LineEpithelial-Mesenchymal TransitionGene Expression RegulationGene Knockdown TechniquesGlycogen Synthase Kinase 3 betaHepatocytesHumansMiceMitochondriaPhospholipases A2RNA, CircularSignal TransductionABHD3 protein, humanGlycogen Synthase Kinase 3 betaHomeodomain ProteinsMEOX1 protein, humanPhospholipases A2RNA, CircularTranscription FactorsTransforming Growth Factor betaTumor Suppressor ProteinsYPEL3 protein, human

Identifiers

PMID40100806
PMCPMC11918346

What Socratic holds

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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.