{
  "abstract": "Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Emerging evidence has established N⁶-methyladenosine (m⁶A) RNA methylation as a key epitranscriptomic mechanism underlying hepatocarcinogenesis. Methyltransferase-like 3 (METTL3), the catalytic core of the m⁶A methyltransferase complex (MTC), forms a heterodimer with METTL14 and cooperates with auxiliary components of the MTC to deposit m⁶A modifications that modulate mRNA stability, splicing, nuclear export, and translation. In this review, we comprehensively summarize the current understanding of METTL3 biology in HCC, focusing on its structure, assembly within the MTC, regulation of coding and non-coding RNAs, and its roles in driving key oncogenic signaling cascades, such as JAK/STAT3, PI3K/AKT/mTOR, Wnt/β-catenin, Hippo/YAP, Notch, Hedgehog, and epithelial-mesenchymal transition. In addition, we discussed how METTL3 remodels the tumor immune microenvironment (TIME) by regulating immune responses and metabolic pathways promoting immune evasion and therapy resistance. Therapeutic strategies targeting METTL3-including small-molecule inhibitors, CRISPR-Cas9 approaches, combination immunotherapy, and tumor-selective delivery systems-are discussed together with the challenges that continue to limit clinical translation. Collectively, these findings position METTL3 as a central epitranscriptomic regulator of HCC progression; however, further mechanistic and clinical validation remains necessary to establish its utility as a therapeutic target and prognostic biomarker.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Marine Bioscience and Environment, College of Ocean Science and Technology, Korea Maritime & Ocean University, Busan 49112, Republic of Korea.",
    "Section of Hematology, Department of Internal Medicine and Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA.",
    "Department of Biochemistry, Kosin University College of Medicine, Seo-Gu, Busan 49267, Republic of Korea.",
    "Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-Ro, Yeongtong-Gu, Suwon 16499, Republic of Korea."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bala Gamage Nalaka Hasith Maduranga",
      "orcid": "0000-0003-3889-1972"
    },
    {
      "affs": [
        1
      ],
      "name": "Hee Doo Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Su In Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Jung Woo Eun",
      "orcid": "0000-0002-2461-6702"
    },
    {
      "affs": [
        0
      ],
      "name": "Sun-Young Lim"
    },
    {
      "affs": [
        2
      ],
      "name": "Hyung Seok Kim",
      "orcid": "0000-0003-2784-0109"
    },
    {
      "affs": [
        2
      ],
      "name": "Jee-Yeong Jeong",
      "orcid": "0000-0001-9482-4526"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/97yg6c2jrmvr4.bib",
  "cited_by": 0,
  "doi": "10.3390/epigenomes10040063",
  "fulltext_url": "https://europepmc.org/articles/PMC13692525",
  "id": "97yg6c2jrmvr4",
  "issns": [
    "2075-4655"
  ],
  "landing_url": "https://europepmc.org/article/MED/42924722",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA modifications and cancer"
    ]
  ],
  "openalex": "W7220449435",
  "pdf_url": "https://europepmc.org/articles/PMC13692525?pdf=render",
  "pmcid": "PMC13692525",
  "pmid": "42924722",
  "published": "2026-10-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/97yg6c2jrmvr4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:36Z",
      "native_id": "MED:42924722",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42924722"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA modifications and cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The Role of METTL3-Mediated m⁶A Methylation in Hepatocellular Carcinoma Progression and Treatment.",
  "title_text": "The Role of METTL3-Mediated m⁶A Methylation in Hepatocellular Carcinoma Progression and Treatment.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:36Z",
  "url": "https://research.draconitic.com/paper/97yg6c2jrmvr4",
  "venue": "Epigenomes",
  "versions": []
}