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As a core component of the m\n                      <jats:sup>6<\/jats:sup>\n                      A methyltransferase complex, METTL14 is known to suppress tumorigenesis; however, its specific role in tumor angiogenesis remains elusive. Given that Vascular Endothelial Growth Factor A (VEGFA) serves as the dominant driver of angiogenesis, we hypothesized that METTL14 may govern VEGFA expression to modulate the vascular niche in hepatocellular carcinoma (HCC).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      This study aimed to elucidate the regulatory axis between METTL14 and VEGFA in HCC. Specifically, we sought to determine whether METTL14 functions as a suppressor of HCC progression by restricting VEGFA\u2010driven angiogenesis through an m\n                      <jats:sup>6<\/jats:sup>\n                      A\u2010dependent mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Quantitative m\n                      <jats:sup>6<\/jats:sup>\n                      A levels were performed to compare modification levels between HCC tissues and paired normal tissues. Bioinformatics analysis was performed to investigate the association between METTL14 and VEGFA expression levels and overall survival (OS) in a cohort of 364 patients with HCC. Immunohistochemistry was conducted to evaluate METTL14 expression in clinical specimens. Functional assays (CCK\u20108, colony formation, and Transwell) were utilized to assess the effects of METTL14 modulation on cell proliferation and metastasis. Western blot analysis confirmed the regulatory effect of METTL14 on VEGFA protein levels. In\u00a0vitro tube formation assays and in\u00a0vivo Matrigel plug assays were performed to evaluate angiogenic capacity. Mechanistic insights were gained using MeRIP\u2010qPCR and RNA Pull\u2010Down Assays to identify m\n                      <jats:sup>6<\/jats:sup>\n                      A modification sites on VEGFA mRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      m\n                      <jats:sup>6<\/jats:sup>\n                      A levels and METTL14 expression were significantly downregulated in HCC tissues. METTL14 knockdown promoted HCC cell proliferation and invasion, whereas overexpression suppressed these phenotypes. Functionally, METTL14 depletion promoted HUVEC tube formation in\u00a0vitro and augmented tumor angiogenesis in\u00a0vivo, effects mechanistically linked to VEGFA upregulation. Mechanistically, METTL14 directly bound to and deposited m\n                      <jats:sup>6<\/jats:sup>\n                      A modifications on VEGFA mRNA, leading to its destabilization and subsequent degradation. Consequently, reduced METTL14 expression resulted in the sustained upregulation of VEGFA in HCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      METTL14 functions as a critical tumor suppressor in HCC by restricting VEGFA\u2010driven angiogenesis via m\n                      <jats:sup>6<\/jats:sup>\n                      A\u2010dependent mRNA destabilization. Our findings uncover a novel epigenetic regulatory mechanism in HCC and identify METTL14 as a potential therapeutic target for anti\u2010angiogenic intervention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70592","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:59:51Z","timestamp":1780070391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methyltransferase\u2010Like 14 Promotes the Angiogenesis of Hepatocellular Carcinoma via Targeting Vascular Endothelial Growth Factor A"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-6646","authenticated-orcid":false,"given":"Xinmiao","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Infectious Disease The Second Hospital of Nanjing, Nanjing University of Chinese Medicine  Nanjing Jiangsu China"},{"name":"The Clinical Infectious 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