{"doi":"10.1111/febs.17097","title":"<scp><i>NEAT1</i></scp> repression by <scp>MED12</scp> creates chemosensitivity in p53 wild‐type breast cancer cells","abstract":"Breast cancer is often treated with chemotherapy. However, the development of chemoresistance results in treatment failure. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to contribute to chemoresistance in breast cancer cells. In studying the transcriptional regulation of NEAT1 using multi-omics approaches, we showed that NEAT1 is up-regulated by 5-fluorouracil in breast cancer cells with wild-type cellular tumor antigen p53 but not in mutant-p53-expressing breast cancer cells. The regulation of NEAT1 involves mediator complex subunit 12 (MED12)-mediated repression of histone acetylation marks at the promoter region of NEAT1. Knockdown of MED12 but not coactivator-associated arginine methyltransferase 1 (CARM1) induced histone acetylation at the NEAT1 promoter, leading to elevated NEAT1 mRNAs, resulting in a chemoresistant phenotype. The MED12-dependent regulation of NEAT1 differs between wild-type and mutant p53-expressing cells. MED12 depletion led to increased expression of NEAT1 in a wild-type p53 cell line, but decreased expression in a mutant p53 cell line. Chemoresistance caused by MED12 depletion can be partially rescued by NEAT1 knockdown in p53 wild-type cells. Collectively, our study reveals a novel mechanism of chemoresistance dependent on MED12 transcriptional regulation of NEAT1 in p53 wild-type breast cancer cells.","journal":"FEBS Journal","year":2024,"id":463114,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":653003,"name":"Eui‐Jun Kim","orcid":"0000-0002-8475-5229","position":1,"is_corresponding":false},{"id":348903,"name":"Junfeng Huang","orcid":"0000-0002-1672-3751","position":2,"is_corresponding":false},{"id":1293363,"name":"Peng Liu","orcid":"0000-0002-2033-3078","position":3,"is_corresponding":false},{"id":651461,"name":"Kristine Donahue","orcid":"0000-0003-3248-7573","position":4,"is_corresponding":false},{"id":299272,"name":"Qinchuan Wang","orcid":"0000-0002-2359-3262","position":5,"is_corresponding":false},{"id":653005,"name":"Yidan Wang","orcid":"0000-0002-0476-6367","position":6,"is_corresponding":false},{"id":275525,"name":"Sean J. McIlwain","orcid":"0000-0002-3820-8400","position":7,"is_corresponding":false},{"id":628796,"name":"Ling Xie","orcid":"0000-0001-8580-0901","position":8,"is_corresponding":false},{"id":11742,"name":"Xian Chen","orcid":"0000-0002-8358-1247","position":9,"is_corresponding":false},{"id":289711,"name":"Lingjun Li","orcid":"0000-0003-0056-3869","position":10,"is_corresponding":false},{"id":579437,"name":"Wei Xu","orcid":"0000-0003-3808-0045","position":11,"is_corresponding":false},{"id":786858,"name":"Shengjie Zhang","orcid":"0000-0002-6250-4752","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:04:28.838123Z","pmid":"38380720","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":[]}