{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:04:08Z","timestamp":1782320648418,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatocellular carcinoma (HCC) remains a lethal malignancy with limited therapeutic options. Kaempferol shows potential in suppressing HCC progression via glycolysis regulation, yet its molecular targets and mechanisms are unclear. Transcriptomic data were analyzed to identify HCC\u2010related DEGs. Intersection with kaempferol's glycolysis\u2010related targets yielded candidate genes. A prognostic risk model was constructed and validated by ROC curves and survival analysis. GSEA and single\u2010cell RNA sequencing explored mechanisms and cellular heterogeneity. Mendelian randomization assessed causality between prognostic genes and HCC. After HCC cells were treated with different concentrations of kaempferol, the effects of kaempferol on proliferation, invasion, and migration of HCC cells were detected by CCK\u20108, cell clone formation, and Transwell cell scratch healing experiments. The expression levels of key proteins in the AKT\u2013mTOR signaling pathway and glycolytic rate\u2010limiting enzymes were detected by Western blot. The spectrophotometric method was used to detect the effect of kaempferol on glucose uptake and lactate production of HCC cells. Finally, the impact of knocking down\n                    <jats:italic>CA9<\/jats:italic>\n                    on glucose uptake and lactic acid production in liver cancer cells was analyzed. The prognostic risk model identified\n                    <jats:italic>GRK6<\/jats:italic>\n                    ,\n                    <jats:italic>ABCC1<\/jats:italic>\n                    ,\n                    <jats:italic>CA9,<\/jats:italic>\n                    and\n                    <jats:italic>CDK5R1<\/jats:italic>\n                    as prognostic genes. GSEA implicated cell cycle and PI3K\u2010Akt pathways in HCC progression driven by these genes. Single\u2010cell analysis revealed pronounced upregulation of prognostic genes in hepatocytes. Finally, MR analysis confirmed that\n                    <jats:italic>CDK5R1<\/jats:italic>\n                    was a risk factor for the incidence of HCC. Kaempferol significantly inhibited the proliferation, invasion, and migration of MHCC97H and Huh7 cells, as well as the expression levels of\n                    <jats:italic>PKM2<\/jats:italic>\n                    ,\n                    <jats:italic>HK2<\/jats:italic>\n                    ,\n                    <jats:italic>p\u2010AKT<\/jats:italic>\n                    ,\n                    <jats:italic>p\u2010mTOR<\/jats:italic>\n                    , and\n                    <jats:italic>p\u2010RPS6<\/jats:italic>\n                    . Kaempferol significantly reduced glucose uptake and lactic acid production in MHCC97H and Huh7 cells. Knockdown of\n                    <jats:italic>CA9<\/jats:italic>\n                    inhibited the uptake of glucose and lactic acid production, along with suppressing the expression of\n                    <jats:italic>HK2<\/jats:italic>\n                    and\n                    <jats:italic>PKM2<\/jats:italic>\n                    in MHCC97H and Huh7 cells. This study found that kaempferol targeted the AKT\u2013mTOR pathway and downregulated the\n                    <jats:italic>CA9<\/jats:italic>\n                    gene, thereby modulating glycolysis and ultimately suppressing the proliferation, invasion, and migration of hepatocellular carcinoma.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600141rr","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T16:05:29Z","timestamp":1781971529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploration of the Key Mechanism by Which Kaempferol Inhibits Glycolysis in Hepatocellular Carcinoma Cells via the\n                    <scp>AKT<\/scp>\n                    \u2013\n                    <scp>mTOR<\/scp>\n                    Pathway"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2158-6514","authenticated-orcid":false,"given":"Han","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Department of Medical Oncology Bengbu Central Hospital  Bengbu China"},{"name":"Anhui Provincial Key Laboratory of Tumor Evolution and Intelligent Diagnosis and Treatment Medical Oncology  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Bengbu Medical University  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Bengbu Central Hospital  Bengbu 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