{"doi":"10.1016/j.drup.2024.101144","title":"Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer","abstract":null,"journal":"Drug Resistance Updates","year":2024,"id":599685,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1536968,"name":"Ya-Chuan Tsai","orcid":null,"position":1,"is_corresponding":false},{"id":1536969,"name":"Ying-Lan Chen","orcid":null,"position":2,"is_corresponding":false},{"id":1452471,"name":"Hui-Kuan Lin","orcid":null,"position":3,"is_corresponding":false},{"id":1536971,"name":"Yun-Chen Huang","orcid":null,"position":4,"is_corresponding":false},{"id":1536972,"name":"Yi-Syuan Lin","orcid":null,"position":5,"is_corresponding":false},{"id":1536973,"name":"Yu-Sheng Cheng","orcid":null,"position":6,"is_corresponding":false},{"id":1536974,"name":"Hsing-Yi Chen","orcid":null,"position":7,"is_corresponding":false},{"id":1536975,"name":"Chia-Jung Li","orcid":null,"position":8,"is_corresponding":false},{"id":1536976,"name":"Tsung-Yen Lin","orcid":null,"position":9,"is_corresponding":false},{"id":1536977,"name":"Shih-Chieh Lin","orcid":null,"position":10,"is_corresponding":false},{"id":1536967,"name":"Shin-Chih Lin","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Un-methylation of NUDT21 represses docosahexaenoic acid biosynthesis contributing to enzalutamide resistance in prostate cancer","abstract":"AIMS: The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive. METHODS: Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function. RESULTS: NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3'UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells. CONCLUSIONS: The un-methylation of NUDT21-mediated 3'UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39208673","pmcid":null,"openalex_id":"https://openalex.org/W4401845623","authors":[],"funders":[{"funder_name":"National Health Research Institutes","grant_id":"NHRI-EX113-11220BI","title":null},{"funder_name":"National Health Research Institutes","grant_id":"NHRI-EX112-11220BI","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC 113-2636-B-006-005","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC 112-2636-B-006-008","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC 111-2636-B-006-012","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC 110-2636-B-006-009","title":null},{"funder_name":"National Science and Technology Council","grant_id":"NSTC 109-2636-B-006-006","title":null}],"total_grants":7,"fwci":4.5681,"citation_percentile":0.95708312,"influential_citations":0,"citation_trend":[{"year":2025,"count":11},{"year":2026,"count":5}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1016/j.drup.2024.101144","host_type":"journal"},{"url":"https://doi.org/10.1016/j.drup.2024.101144","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S136876462400102X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S136876462400102X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39208673","host_type":"repository"}],"fields_of_study":["Prostate Cancer Treatment and Research","Epigenetics and DNA Methylation","Cancer, Hypoxia, and Metabolism","Phenylthiohydantoin","Male","Animals","Nitriles","Humans","Drug Resistance, Neoplasm","Benzamides","Mice","Cell Line, Tumor","Docosahexaenoic Acids","Methylation","Mice, Transgenic","Prostatic Neoplasms, Castration-Resistant","Prostatic Neoplasms","Gene Expression Regulation, Neoplastic","Antineoplastic Agents"],"mesh_terms":["Animals","Antineoplastic Agents","Benzamides","Docosahexaenoic Acids","Humans","Male","Methylation","Mice, Transgenic","Nitriles","Phenylthiohydantoin","Prostatic Neoplasms","Gene Expression Regulation, Neoplastic","Drug Resistance, Neoplasm","Cell Line, Tumor","Mice","Prostatic Neoplasms, Castration-Resistant"],"keywords":["Enzalutamide","Prostate cancer","Androgen receptor","Cancer research","Methylation","Cancer","Medicine","Biology","Internal medicine","Gene","Genetics","Mono-methylation","Nudt21","Enzalutamide Resistance","3’Utr Usage Switch","Cuproptosis Insensitivity And Dha"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T11:00:03.590764Z","pmid":null,"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":[]}