{"doi":"10.1016/j.molcel.2023.06.024","title":"A lncRNA from the FTO locus acts as a suppressor of the m6A writer complex and p53 tumor suppression signaling","abstract":"N6-methyladenosine (m6A) of mRNAs modulated by the METTL3-METTL14-WTAP-RBM15 methyltransferase complex and m6A demethylases such as FTO play important roles in regulating mRNA stability, splicing, and translation. Here, we demonstrate that FTO-IT1 long noncoding RNA (lncRNA) was upregulated and positively correlated with poor survival of patients with wild-type p53-expressing prostate cancer (PCa). m6A RIP-seq analysis revealed that FTO-IT1 knockout increased mRNA m6A methylation of a subset of p53 transcriptional target genes (e.g., FAS, TP53INP1, and SESN2) and induced PCa cell cycle arrest and apoptosis. We further showed that FTO-IT1 directly binds RBM15 and inhibits RBM15 binding, m6A methylation, and stability of p53 target mRNAs. Therapeutic depletion of FTO-IT1 restored mRNA m6A level and expression of p53 target genes and inhibited PCa growth in mice. Our study identifies FTO-IT1 lncRNA as a bona fide suppressor of the m6A methyltransferase complex and p53 tumor suppression signaling and nominates FTO-IT1 as a potential therapeutic target of cancer.","journal":"Molecular Cell","year":2023,"id":320437,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243016,"name":"Jiangbo Wei","orcid":"0000-0003-2691-6490","position":1,"is_corresponding":false},{"id":445255,"name":"Rui Sun","orcid":"0000-0003-4054-1365","position":2,"is_corresponding":false},{"id":640536,"name":"Haoyue Sheng","orcid":"0000-0002-1707-6621","position":3,"is_corresponding":false},{"id":35913,"name":"Kai Yin","orcid":"0000-0002-3351-4222","position":4,"is_corresponding":false},{"id":632840,"name":"Yunqian Pan","orcid":"0000-0003-0912-8978","position":5,"is_corresponding":false},{"id":640537,"name":"Rafael E. Jiménez","orcid":"0000-0003-2348-0214","position":6,"is_corresponding":false},{"id":86004,"name":"Sujun Chen","orcid":"0000-0002-1941-3951","position":7,"is_corresponding":false},{"id":1031063,"name":"Xiao‐Long Cui","orcid":"0000-0001-9000-1792","position":8,"is_corresponding":false},{"id":274848,"name":"Zhongyu Zou","orcid":"0000-0001-7152-5435","position":9,"is_corresponding":false},{"id":1031064,"name":"Zhiying Yue","orcid":"0009-0007-6777-3488","position":10,"is_corresponding":false},{"id":736429,"name":"Michael J. Emch","orcid":"0000-0001-8670-8138","position":11,"is_corresponding":false},{"id":351330,"name":"John R. Hawse","orcid":"0000-0003-3406-470X","position":12,"is_corresponding":false},{"id":392452,"name":"Liguo Wang","orcid":"0000-0003-2072-4826","position":13,"is_corresponding":false},{"id":453056,"name":"Housheng Hansen He","orcid":"0000-0003-2898-3363","position":14,"is_corresponding":false},{"id":1031065,"name":"Shujie Xia","orcid":"0000-0002-2293-3157","position":15,"is_corresponding":false},{"id":1031066,"name":"Bangmin Han","orcid":"0000-0001-9101-8377","position":16,"is_corresponding":false},{"id":21408,"name":"Chuan He","orcid":"0000-0003-4319-7424","position":17,"is_corresponding":false},{"id":409827,"name":"Haojie Huang","orcid":"0000-0003-2751-6413","position":18,"is_corresponding":false},{"id":894307,"name":"Jianong Zhang","orcid":"0000-0001-7700-215X","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T01:07:22.377587Z","pmid":"37478845","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}