{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:34:26Z","timestamp":1781714066267,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute myeloid leukemia (AML) remains a clinical challenge with suboptimal long-term survival. While circular RNAs derived from the RNF220 host gene have been implicated in AML pathogenesis, the functional role and regulatory mechanisms of RNF220 itself in AML are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated bioinformatics analyses of public databases (TCGA-LAML, TARGET-LAML) and local cohort with\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays. RNF220 was knocked down and overexpressed in AML cell lines using lentivirus. Transcriptomic profiling (RNA-seq), metabolic pathway enrichment (GSVA, GSEA), and immune microenvironment deconvolution (xCELL, CIBERSORT, MCP-counter) were performed. Transcription factor binding sites were predicted across five databases (JASPAR, ENCODE, GTRD, etc.). Validation of transcriptional regulation was performed using ChIP-PCR and luciferase reporter assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      RNF220 overexpression correlated with poor prognosis in AML, drove an immunosuppressive microenvironment characterized by reduced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and inhibited NK activity and M2 polarization of macrophage. RNF220 promoted tumor proliferation by suppressing apoptosis and preventing G1 arrest. Knockdown of RNF220 dysregulated metabolic pathways, notably suppressing glycolysis and phenylalanine metabolism. Mechanistically, FOXA1 was identified as an upstream negative regulator of RNF220, where high FOXA1 predicted favorable survival and inversely correlated with RNF220-associated metabolic reprogramming.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NF220 acts as an oncogenic ubiquitin ligase in AML by coordinating dual pro-leukemic mechanisms: cell-intrinsic metabolic rewiring (glycolysis\/phenylalanine) and immune evasion via microenvironment suppression. Targeting the FOXA1\u2013RNF220 axis may offer novel therapeutic strategies for high-risk AML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1670895","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:24:22Z","timestamp":1761801862000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Dual oncogenic role of RNF220 in AML: linking metabolic rewiring to cell proliferation and immune evasion"],"prefix":"10.3389","volume":"15","author":[{"given":"Bixia","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qitian","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifang","family":"Ouyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-007-9097-2","article-title":"Patterns of leukemia incidence in the United States by subtype and demographic characteristics, 1997-2002","volume":"19","author":"Yamamoto","year":"2008","journal-title":"Cancer Causes Control"},{"key":"B2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.450","article-title":"Incidence of haematological Malignancy by sub-type: a report from the Haematological Malignancy Research Network","volume":"105","author":"Smith","year":"2011","journal-title":"Br J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-282632","article-title":"Incidence of hematologic Malignancies in Europe by morphologic subtype: results of the HAEMACARE project","volume":"116","author":"Sant","year":"2010","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1182\/blood-2011-04-347872","article-title":"Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007","volume":"119","author":"Dores","year":"2012","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1182\/blood-2015-08-604520","article-title":"An update of current treatments for adult acute myeloid leukemia","volume":"127","author":"Dombret","year":"2016","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.2208","article-title":"Genomics of acute myeloid leukemia diagnosis and pathways","volume":"35","author":"Bullinger","year":"2017","journal-title":"J Clin Oncol"},{"key":"B8","first-page":"29","article-title":"Gene mutations and molecularly targeted therapies in acute myeloid leukemia","volume":"3","author":"Hatzimichael","year":"2013","journal-title":"Am J Blood Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2022.280802","article-title":"Update on current treatments for adult acute myeloid leukemia: to treat acute myeloid leukemia intensively or non-intensively? 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