{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:16:24Z","timestamp":1780478184105,"version":"3.54.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) represents a highly prevalent metabolic disorder; however, the functional role of mitogen-activated protein kinase 10 (MAPK10) in the initiation and progression of NAFLD remains incompletely understood. This study investigated MAPK10\u2019s role in NAFLD and its regulatory mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Bioinformatics analysis was performed on the GSE89632 dataset to screen for differentially expressed genes (DEGs) associated with NAFLD. An in vivo NAFLD model was established in C57BL\/6\u00a0J mice by feeding a high-fat diet (HFD), and subsequent lentiviral transduction was used to achieve hepatic overexpression or knockdown of MAPK10 and DNA methyltransferase 1 (DNMT1). In vitro, HepG2 cells were transfected with DNMT1 overexpression plasmids. Molecular analyses, including RT-qPCR and Western blot, were used to measure gene and protein expression levels. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were employed to assess the m5C modification of MAPK10 mRNA and its transcriptional activity, respectively. An RNA stability assay was used to evaluate mRNA half-life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MAPK10 expression was significantly reduced in the liver tissues of HFD-fed mice. Overexpression of MAPK10 alleviated hepatic steatosis, oxidative stress, and mitochondrial damage in vivo. Mechanistically, DNMT1 enhanced MAPK10 expression and stability in an m5C-dependent manner. RIP assay confirmed increased m5C modification of MAPK10 mRNA upon DNMT1 overexpression. Luciferase reporter assay demonstrated that DNMT1 specifically enhanced the activity of wild-type, but not m5C-site-mutated, MAPK10. RNA stability assay further showed that DNMT1 overexpression stabilized MAPK10 mRNA. Rescue experiments indicated that MAPK10 knockdown reversed the protective effects (improved lipid accumulation, oxidative stress, and mitochondrial function) induced by DNMT1 overexpression in HFD-fed mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MAPK10 plays a protective role in NAFLD by ameliorating hepatic steatosis and mitochondrial dysfunction. Its expression is positively regulated by DNMT1 via m5C-mediated RNA stabilization. This study highlights the DNMT1-MAPK10 axis as a potential therapeutic target for NAFLD.<\/jats:p>\n                    <jats:p>Insight Box This study uncovers a previously unrecognized RNA epigenetic regulatory axis in NAFLD, demonstrating that DNMT1 post-transcriptionally regulates MAPK10 expression and stability through m5C RNA methylation. We establish MAPK10 as a key metabolic protector against NAFLD, ameliorating hepatic steatosis, oxidative stress, and mitochondrial dysfunction. By integrating bioinformatics, molecular biology, and functional validation across in vivo and in vitro models, we delineate a mechanistic pathway where m5C modification critically modulates MAPK10 activity. These findings not only provide fresh insight into the RNA-centric regulatory layer of NAFLD pathogenesis but also spotlight the therapeutic potential of modulating the DNMT1-MAPK10 axis, underscoring the value of integrative research strategies in elucidating complex metabolic diseases. Main points MAPK10 expression was significantly reduced in the liver tissues of HFD-induced NAFLD mice. MAPK10 overexpression alleviated hepatic steatosis and mitochondrial damage in HFD-fed mice. DNMT1 positively regulates MAPK10 expression and mRNA stability in an m5C RNA methylation-dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/intbio\/zyag006","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T12:35:03Z","timestamp":1772195703000},"source":"Crossref","is-referenced-by-count":0,"title":["DNMT1 stabilizes MAPK10\n                    <i>via<\/i>\n                    m5C RNA methylation to ameliorate hepatic steatosis and mitochondrial dysfunction in non-alcoholic fatty liver disease"],"prefix":"10.1093","volume":"18","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"Guizhou University of Traditional Chinese Medicine , No. 4, Dongqing Road, Huaxi University Town, Huaxi District, Guiyang City, Guizhou Province 550025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department 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