METTLING in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses through distinct stages from hepatic lipid deposition or steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and ultimately to cirrhosis or hepatocellular carcinoma (HCC). The pathogenesis of MASLD is dynamically regulated by epigenetic remodeling, among which the methyltransferase-like (METTL) family acts as a master regulator, coordinating multi-tiered pathological processes including modulating lipid homeostasis in hepatocytes, amplifying inflammatory signaling in Kupffer cells, driving fibrotic activation in stellate cells, and promoting malignant transformation via epigenetic reprogramming. By systematically deciphering the molecular interactome of the METTL family across hepatic cellular heterogeneity, this review aims to clarify hierarchical regulatory architecture governing the pathogenesis of MASLD and discuss precision epigenetic editing-based therapeutic paradigms.

• Publication year

  2025

• Venue

  Life Science

• Publication date

  2025-11-09

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.lfs.2025.124082PMID 41218656
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• METTL14‐Induced M6A Methylation Increases G6pc Biosynthesis, Hepatic Glucose Production and Metabolic Disorders in Obesity

  2025cited by this paper
• Molecular mechanisms in MASLD/MASH related HCC.

  2024cited by this paper
• METTL3/16-mediated m6A modification of ZNNT1 promotes hepatocellular carcinoma progression by activating ZNNT1/osteopontin/S100A9 positive feedback loop-mediated crosstalk between macrophages and tumour cells.

  2024cited by this paper
• METTL16 promotes liver cancer stem cell self-renewal via controlling ribosome biogenesis and mRNA translation

  2024cited by this paper
• Discovery of a PROTAC degrader for METTL3-METTL14 complex.

  2024cited by this paper
• Patent landscape of small molecule inhibitors of METTL3 (2020-present)

  2024cited by this paper
• METTL14 downregulation drives S100A4+ monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression

  2024cited by this paper
• A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

  2024cited by this paper
• m6A methyltransferase METTL14‑mediated RP1‑228H13.5 promotes the occurrence of liver cancer by targeting hsa‑miR‑205/ZIK1

  2024cited by this paper
• The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression

  2024cited by this paper
• Mettl3-mediated m 6 A modification plays a role in lipid metabolism disorders and progressive liver damage in mice by regulating lipid metabolism-related gene expression

  2023cited by this paper
• METTL5 serves as a diagnostic and prognostic biomarker in hepatocellular carcinoma by influencing the immune microenvironment

  2023cited by this paper
• A multi-society Delphi consensus statement on new fatty liver disease nomenclature.

  2023cited by this paper
• METTL3-mediated m6A mRNA modification was involved in cadmium-induced liver injury.

  2023cited by this paper
• METTL3 and STAT3 form a positive feedback loop to promote cell metastasis in hepatocellular carcinoma

  2023cited by this paper
• Changing epidemiology, global trends and implications for outcomes of NAFLD.

  2023cited by this paper
• CYP4F2 is a human-specific determinant of circulating N-acyl amino acid levels

  2023cited by this paper
• m6A-mediated gluconeogenic enzyme PCK1 upregulation protects against hepatic ischemia-reperfusion injury

  2023cited by this paper
• METTL9-SLC7A11 axis promotes hepatocellular carcinoma progression through ferroptosis inhibition

  2023cited by this paper
• Therapeutic effect and transcriptome-methylome characteristics of METTL3 inhibition in liver hepatocellular carcinoma

  2023cited by this paper
• Emerging role of N6-methyladenosine (m6A) in the homeostasis of glucose metabolism.

  2023cited by this paper
• Silencing METTL14 alleviates liver injury in non-alcoholic fatty liver disease by regulating mitochondrial homeostasis

  2023cited by this paper
• METTL3 drives NAFLD-related hepatocellular carcinoma and is a therapeutic target for boosting immunotherapy

  2023cited by this paper
• METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2–dependent mechanism

  2023cited by this paper
• Adipose METTL14‐Elicited N6‐Methyladenosine Promotes Obesity, Insulin Resistance, and NAFLD Through Suppressing β Adrenergic Signaling and Lipolysis

  2023cited by this paper
• Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism

  2023cited by this paper
• Mettl3-mediated m6A modification plays a role in lipid metabolism disorders and progressive liver damage in mice by regulating lipid metabolism-related gene expression

  2023cited by this paper
• METTL3-m6A-EGFR-axis drives lenvatinib resistance in hepatocellular carcinoma.

  2023cited by this paper
• METTL5 stabilizes c‐Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression

  2023cited by this paper
• Dysregulated m6A Modification Promotes Lipogenesis and Development of Non-alcoholic Fatty Liver Disease and Hepatocellular Carcinoma.

  2022cited by this paper
• Novel insights into the N6-methyladenosine RNA modification and phytochemical intervention in lipid metabolism.

  2022cited by this paper
• METTL1-mediated m7G tRNA modification promotes lenvatinib resistance in hepatocellular carcinoma.

  2022cited by this paper
• Hepatocellular carcinoma

  2022cited by this paper
• METTL3 promotes m6A hypermethylation of RBM14 via YTHDF1 leading to the progression of hepatocellular carcinoma

  2022cited by this paper
• N6-methyladenosine (m6A) in 18S rRNA promotes fatty acid metabolism and oncogenic transformation

  2022cited by this paper
• Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

  2022cited by this paper
• The m6A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis.

  2022cited by this paper
• The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis.

  2022cited by this paper
• Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease - novel insights into cellular communication circuits.

  2022cited by this paper
• UniProt: the Universal Protein Knowledgebase in 2023

  2022cited by this paper
• METTL16 exerts an m6A-independent function to facilitate translation and tumorigenesis

  2022cited by this paper
• METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner

  2022cited by this paper
• METTL3‐mediated maturation of miR‐589‐5p promotes the malignant development of liver cancer

  2022cited by this paper
• The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression

  2021cited by this paper
• Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B

  2021cited by this paper
• HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation

  2021cited by this paper
• Human METTL7B is an alkyl thiol methyltransferase that metabolizes hydrogen sulfide and captopril

  2021cited by this paper
• Mettl14-Mediated m6A Modification Facilitates Liver Regeneration by Maintaining Endoplasmic Reticulum Homeostasis

  2021cited by this paper
• Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia

  2021cited by this paper
• USP48 Is Upregulated by Mettl14 to Attenuate Hepatocellular Carcinoma via Regulating SIRT6 Stabilization

  2021cited by this paper
• Mechanisms and disease consequences of nonalcoholic fatty liver disease.

  2021cited by this paper
• METTL3/METTL14 Transactivation and m6A-Dependent TGF-β1 Translation in Activated Kupffer Cells

  2021cited by this paper
• Identification METTL18 as a Potential Prognosis Biomarker and Associated With Immune Infiltrates in Hepatocellular Carcinoma

  2021cited by this paper
• Liver regeneration and inflammation: from fundamental science to clinical applications

  2021cited by this paper
• Acute depletion of METTL3 implicates N6-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome

  2021cited by this paper
• RNA methyltransferase METTL16: Targets and function

  2021cited by this paper
• Pathophysiological Communication between Hepatocytes and Non-Parenchymal Cells in Liver Injury from NAFLD to Liver Fibrosis.

  2021cited by this paper
• METTL3‐mediated m6A methylation of ASPM drives hepatocellular carcinoma cells growth and metastasis

  2021cited by this paper
• METTL3-m6A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease.

  2021cited by this paper
• m6A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity

  2021cited by this paper
• The METTL3/MALAT1/PTBP1/USP8/TAK1 axis promotes pyroptosis and M1 polarization of macrophages and contributes to liver fibrosis

  2021cited by this paper
• HRD1-mediated METTL14 degradation regulates m6A mRNA modification to suppress ER proteotoxic liver disease.

  2021cited by this paper
• Current and Potential Therapies Targeting Inflammation in NASH

  2021cited by this paper
• N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA

  2021cited by this paper
• METTL1 promotes hepatocarcinogenesis via m7G tRNA modification‐dependent translation control

  2021cited by this paper
• Downregulation of METTL6 mitigates cell progression, migration, invasion and adhesion in hepatocellular carcinoma by inhibiting cell adhesion molecules

  2021cited by this paper
• METTL3 facilitates the progression of hepatocellular carcinoma by modulating the m6A level of USP7.

  2021cited by this paper
• METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice

  2020cited by this paper
• RNA m6A methylation regulates sorafenib resistance in liver cancer through FOXO3‐mediated autophagy

  2020cited by this paper
• miR-328-3p overexpression attenuates the malignant proliferation and invasion of liver cancer via targeting Endoplasmic Reticulum Metallo Protease 1 to inhibit AKT phosphorylation

  2020cited by this paper
• METTL14 Inhibits Hepatocellular Carcinoma Metastasis Through Regulating EGFR/PI3K/AKT Signaling Pathway in an m6A-Dependent Manner

  2020cited by this paper
• Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention

  2020cited by this paper
• HBXIP drives metabolic reprogramming in hepatocellular carcinoma cells via METTL3‐mediated m6A modification of HIF‐1α

  2020cited by this paper
• Analysis of METTL3 and METTL14 in hepatocellular carcinoma

  2020cited by this paper
• Molecular and cellular mechanisms of liver fibrosis and its regression

  2020cited by this paper
• Serum miR-885-5p can be used as a marker for efficacy prediction and prognosis of advanced liver cancer.

  2020cited by this paper
• Chemokines in Non-alcoholic Fatty Liver Disease: A Systematic Review and Network Meta-Analysis

  2020cited by this paper
• RNA m6A methylation promotes the formation of vasculogenic mimicry in hepatocellular carcinoma via Hippo pathway

  2020cited by this paper
• Nonalcoholic Steatohepatitis: A Review.

  2020cited by this paper
• Identification of NOVA family proteins as novel β-catenin RNA-binding proteins that promote epithelial-mesenchymal transition

  2020cited by this paper
• Silencing lncRNA Lfar1 alleviates the classical activation and pyoptosis of macrophage in hepatic fibrosis

  2020cited by this paper
• METTL3 expression is associated with glycolysis metabolism and sensitivity to glycolytic stress in hepatocellular carcinoma

  2020cited by this paper
• M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

  2020cited by this paper
• miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy.

  2020cited by this paper
• METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth

  2020cited by this paper
• A new definition for metabolic associated fatty liver disease: an international expert consensus statement.

  2020cited by this paper
• METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism.

  2019cited by this paper
• METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN

  2019cited by this paper
• YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma.

  2019cited by this paper
• Deciphering Determinants in Ribosomal Methyltransferases That Confer Antimicrobial Resistance.

  2019cited by this paper
• The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

  2019cited by this paper
• Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases

  2019cited by this paper
• RNA N6‐methyladenosine methyltransferase‐like 3 promotes liver cancer progression through YTHDF2‐dependent posttranscriptional silencing of SOCS2

  2018cited by this paper
• Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

  2018cited by this paper
• Emerging role and therapeutic implication of Wnt signaling pathways in liver fibrosis.

  2018cited by this paper
• Carnitine palmitoyltransferase 1C regulates cancer cell senescence through mitochondria-associated metabolic reprograming

  2018cited by this paper
• Circadian Clock Regulation of Hepatic Lipid Metabolism by Modulation of m6A mRNA Methylation.

  2018cited by this paper
• Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling.

  2017cited by this paper
• Mechanisms of hepatic stellate cell activation

  2017cited by this paper
• Liver macrophages in tissue homeostasis and disease

  2017cited by this paper

• No citing papers are available for this paper.