{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T10:10:06Z","timestamp":1749377406157,"version":"3.41.0"},"reference-count":0,"publisher":"Termedia Sp. z.o.o.","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Med Sci"],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Inhibited acute myeloid leukemia (AML) proliferation is accompanied by downregulated peroxisome proliferator-activated receptor alpha (PPAR\u03b1), which however can be stabilized via sumoylation. This study investigated how PPAR\u03b1 sumoylation impacts on AML cell growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Human AML HL-60 and tohoku hospital pediatrics-1 (THP-1) cells were treated with the PPAR\u03b1 inhibitor, GW6471 (10 \u00b5M), for 24 and 48 h. THP-1 cells were exposed to the PPAR\u03b1 agonist, pirinixic acid (10 \u00b5M), after the expression of the small ubiquitin-like modifier proteins (SUMO)-conjugating enzyme UBC9 was manipulated. The interaction between PPAR\u03b1 and SUMO1 was detected by immunoprecipitation assay. HL-60 and THP-1 cell viability, apoptosis and ferroptosis were measured via cell counting kit-8 assay, flow cytometry, BODIPY-C11 staining and\/or colorimetric assay. UBC9, glutathione peroxidase 4 (GPX4), recombinant solute carrier family 7, member 11(SLC7A11) and PPAR\u03b1 expressions were analyzed by qRT-PCR or Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GW6471 treatment for 24 and 48 h suppressed viability, promoted apoptosis and lipid peroxidation, increased the level of Fe2+, and decreased the expressions of GPX4, SLC7A11 and PPAR\u03b1 in HL-60\/THP-1 cells. PPAR\u03b1 antibody induced enrichment of PPAR\u03b1 and SUMO1 in THP-1 cells, which was attenuated after UBC9 silencing. UBC9 silencing resulted in viability decrease, apoptosis and lipid peroxidation promotion, Fe2+ upregulation, and GPX4, SLC7A11 and PPAR\u03b1 downregulation in THP-1 cells, which were all counteracted by pirinixic acid.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>UBC9 silencing-induced PPAR\u03b1 desumoylation induces suppression of AML cell growth by ferroptosis.<\/jats:p><\/jats:sec>","DOI":"10.5114\/aoms\/204235","type":"journal-article","created":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T09:47:03Z","timestamp":1749376023000},"source":"Crossref","is-referenced-by-count":0,"title":["UBC9 silencing-mediated PPAR\u03b1 desumoylation induces inhibition of cell proliferation by ferroptosis in acute myeloid leukemia"],"prefix":"10.5114","author":[{"given":"Xiaolu","family":"Song","sequence":"first","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Shi","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaogang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Peng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huafang","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lai","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianping","family":"Lan","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, Affiliated People\u2019s Hospital, Hangzhou Medical College, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3061","published-online":{"date-parts":[[2025,6,8]]},"container-title":["Archives of Medical Science"],"original-title":[],"link":[{"URL":"https:\/\/www.archivesofmedicalscience.com\/pdf-204235-125942","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.archivesofmedicalscience.com\/pdf-204235-125942","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T09:47:06Z","timestamp":1749376026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.archivesofmedicalscience.com\/UBC9-silencing-mediated-PPAR-desumoylation-induces-inhibition-of-cell-proliferation,204235,0,2.html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,8]]},"references-count":0,"alternative-id":["204235"],"URL":"https:\/\/doi.org\/10.5114\/aoms\/204235","relation":{},"ISSN":["1734-1922","1896-9151"],"issn-type":[{"value":"1734-1922","type":"print"},{"value":"1896-9151","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,8]]}}}