{"doi":"10.1016/j.drup.2025.101344","title":"DEAF1 confers resistance to adriamycin-induced apoptosis and pyroptosis in multiple myeloma","abstract":null,"journal":"Drug Resistance Updates","year":2026,"id":635119,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":1647595,"name":"Yongxin Wei","orcid":null,"position":1,"is_corresponding":false},{"id":1058303,"name":"Shuang Liu","orcid":"0000-0003-4889-9142","position":2,"is_corresponding":false},{"id":625526,"name":"Lu Chen","orcid":"0000-0003-2906-2507","position":3,"is_corresponding":false},{"id":1647596,"name":"Xuhui Wang","orcid":null,"position":4,"is_corresponding":false},{"id":1302623,"name":"Zihao Liu","orcid":"0009-0007-5921-7684","position":5,"is_corresponding":false},{"id":292715,"name":"Lingling Liu","orcid":"0000-0003-0039-7098","position":6,"is_corresponding":false},{"id":1118078,"name":"Yaohui Wang","orcid":"0000-0002-1486-5262","position":7,"is_corresponding":false},{"id":1647597,"name":"Xinyu Lv","orcid":null,"position":8,"is_corresponding":false},{"id":1647599,"name":"Shanliang Sun","orcid":null,"position":9,"is_corresponding":false},{"id":1647601,"name":"Haiwen Ni","orcid":null,"position":10,"is_corresponding":false},{"id":1647603,"name":"Chunyan Gu","orcid":null,"position":11,"is_corresponding":false},{"id":707835,"name":"Ye Yang","orcid":"0000-0003-0228-5102","position":12,"is_corresponding":false},{"id":1647594,"name":"Zhendong Deng","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"DEAF1 confers resistance to adriamycin-induced apoptosis and pyroptosis in multiple myeloma","abstract":"<h4>Aims</h4>Transcriptional dysregulation by aberrant transcription factors (TFs) is a key driver of drug resistance. Resistance to adriamycin (ADR) frequently develops following first-line treatment for multiple myeloma (MM). This study aims to identify novel TFs associated with ADR resistance in MM and to elucidate their underlying mechanisms.<h4>Methods</h4>We employed a protein chip assay with FITC-labeled celastrol and identified the deformed epidermal autoregulatory factor 1 (DEAF1) as a potential target in MM. High-throughput sequencing was performed to identify DEAF1 downstream targets. Both in vivo and in vitro models were utilized to delineate the role of DEAF1 in MM cell proliferation and ADR resistance.<h4>Results</h4>High DEAF1 expression was associated with poor prognosis in MM patients, and was found to promote MM cell proliferation and induce ADR resistance. Mechanistically, DEAF1 directly binds to the RAD50 promoter via its SAND domain, upregulating RAD50 expression and consequently activating the ATM pathway. Furthermore, DEAF1 recruited AP-2-alpha (AP-2α) through its MYND domain, leading to the downregulation of tyrosine-protein kinase Fer (FER). This downregulation impaired FER-mediated phosphorylation of GSDME, which is known to enhance the cleavage efficiency of GSDME by caspase-3. Additionally, celastrol synergized with ADR to inhibit MM cell viability by disrupting the binding of DEAF1 to the promoters of its target genes.<h4>Conclusions</h4>Our findings demonstrate that DEAF1 attenuates ADR-induced apoptosis and pyroptosis in MM by enhancing DNA damage repair and suppressing GSDME cleavage via the FER/GSDME axis. This study provides a novel therapeutic target for the treatment of MM.","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41421151","pmcid":null,"openalex_id":"https://openalex.org/W4417399391","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82341230","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82404735","title":null},{"funder_name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","grant_id":"","title":null}],"total_grants":3,"fwci":0.4868,"citation_percentile":0.7031318,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"closed","license":"https://doi.org/10.15223/policy-004","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1368764625001475?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1368764625001475?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.drup.2025.101344","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41421151","host_type":"repository"}],"fields_of_study":["Inflammasome and immune disorders","Cell death mechanisms and regulation","Cancer Mechanisms and Therapy","Humans","Multiple Myeloma","Drug Resistance, Neoplasm","Doxorubicin","Apoptosis","Animals","Pyroptosis","Cell Line, Tumor","Mice","Cell Proliferation","Gene Expression Regulation, Neoplastic","DNA-Binding Proteins","Antibiotics, Antineoplastic","Xenograft Model Antitumor Assays"],"mesh_terms":["Pyroptosis","Animals","Antibiotics, Antineoplastic","DNA-Binding Proteins","Doxorubicin","Humans","Multiple Myeloma","Gene Expression Regulation, Neoplastic","Apoptosis","Drug Resistance, Neoplasm","Xenograft Model Antitumor Assays","Cell Line, Tumor","Cell Proliferation","Mice"],"keywords":["Pyroptosis","Apoptosis","Multiple myeloma","DNA damage","DNA","Cleavage (geology)","Poly ADP ribose polymerase","Adriamycin Resistance","Deformed Epidermal Autoregulatory Factor 1"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:40:20.883386Z","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":[]}