{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:53:42Z","timestamp":1775714022299,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007620","name":"Department of Education of Liaoning Province","doi-asserted-by":"publisher","award":["LJ212410160048"],"award-info":[{"award-number":["LJ212410160048"]}],"id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Metabolic reprogramming is a hallmark of glioblastoma multiforme (GBM), with lactate dehydrogenase A (LDHA) playing a key role in aerobic glycolysis. However, the upstream transcriptional mechanisms driving LDHA overexpression in GBM remain poorly understood. This study aims to investigate the transcriptional regulatory network governing LDHA-mediated glycolysis and to explore the functional roles of KLF1 and NFYC in GBM progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bioinformatic analysis of The Cancer Genome Atlas data was performed to assess LDHA, KLF1, and NFYC expression in glioma. glioblastoma multiforme cell lines were used for loss- and gain-of-function studies by siRNA\/shRNA knockdown and overexpression, including assessments of glycolytic flux, mitochondrial metabolism, cell proliferation, and apoptosis Metabolic activity was assessed using Seahorse extracellular flux analysis. Transcriptional regulation was evaluated by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Tumor growth was assessed in a subcutaneous xenograft model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LDHA was significantly upregulated in GBM and associated with poor prognosis. LDHA knockdown suppressed tumor growth, glycolysis, mitochondrial respiration, and induced apoptosis. KLF1 was identified as a direct transcriptional activator of LDHA. NFYC was shown to bind the KLF1 promoter and positively regulate its expression. Functional studies demonstrated that the NFYC-KLF1-LDHA axis promotes GBM cell proliferation, inhibits apoptosis, and enhances glycolytic and mitochondrial metabolism. The oncogenic effects of NFYC were partially reversed by KLF1 knockdown, and\n                      <jats:italic>vice versa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals a novel hierarchical transcriptional pathway in which NFYC regulates KLF1, which in turn activates LDHA, driving aerobic glycolysis and tumor progression in GBM. Targeting the NFYC-KLF1-LDHA axis may represent a promising therapeutic strategy for glioblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1810731","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:21:35Z","timestamp":1775712095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["NFYC upregulates KLF1 expression and activate LDHA to drive glycolysis and tumor growth in glioblastoma cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Yan","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Anatomy, College of Basic Medical Sciences, Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, College of Basic Medical Sciences, Jinzhou Medical University","place":["Jinzhou, China"]},{"name":"Liaoning Provincial Key Laboratory of Neurodegenerative Diseases","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilu","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Basic Medical Sciences, Jinzhou Medical University","place":["Jinzhou, China"]},{"name":"Liaoning Provincial Key Laboratory of Neurodegenerative Diseases","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Basic Medical Sciences, Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weimin","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15787","DOI":"10.3390\/ijms242115787","article-title":"The warburg effect explained: integration of enhanced glycolysis with heterogeneous mitochondria to promote cancer cell proliferation","volume":"24","author":"Alberghina","year":"2023","journal-title":"Int. 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