{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Qiao Y"],"funding":["National Nature Science Foundation of China","Natural Science Foundation of Tianjin","the Fundamental Research Funds for the Central Universities, Nankai University","Beijing Science and Technology Innovation Medical Development Foundation","Beijing-Tianjin-Hebei Basic Research Cooperation Project"],"pagination":["108"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11005233"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(1)"],"pubmed_abstract":["Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m<sup>6</sup>A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m<sup>6</sup>A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m<sup>6</sup>A modification is increased during ferroptotic cell death and correlates with the decreased m<sup>6</sup>A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m<sup>6</sup>A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression."],"journal":["Journal of experimental & clinical cancer research : CR"],"pubmed_title":["Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression."],"pmcid":["PMC11005233"],"funding_grant_id":["KC2021-JX-0186-78","82373906, 81973356","63231108, ZB22010404, 63213082 and 92122017","21JCZDJC00060","21JCYBJC00180","81672781","23JCZXJC00020"],"pubmed_authors":["Liu H","Liu L","Li C","Wang C","Su M","Zhang S","Shan C","Wang J","Zhang Q","Dai X","Sun M","Qiao Y","Li Z","Fan J","Sun H","Xue J","Zhang C","Situ F","Zhao H","Liu G","Jia Z"],"additional_accession":[]},"is_claimable":false,"name":"Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.","description":"Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m<sup>6</sup>A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m<sup>6</sup>A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m<sup>6</sup>A modification is increased during ferroptotic cell death and correlates with the decreased m<sup>6</sup>A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m<sup>6</sup>A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-06-01T11:28:52.545Z","creation":"2026-04-08T11:53:10.476Z"},"accession":"S-EPMC11005233","cross_references":{"pubmed":["38600610"],"doi":["10.1186/s13046-024-03032-9"]}}