{"doi":"10.1002/1878-0261.13478","title":"Functional inhibition of the <scp>RNA</scp>‐binding protein <scp>HuR</scp> sensitizes triple‐negative breast cancer to chemotherapy","abstract":"Chemotherapy remains the standard treatment for triple-negative breast cancer (TNBC); however, chemoresistance compromises its efficacy. The RNA-binding protein Hu antigen R (HuR) could be a potential therapeutic target to enhance the chemotherapy efficacy. HuR is known to mainly stabilize its target mRNAs, and/or promote the translation of encoded proteins, which are implicated in multiple cancer hallmarks, including chemoresistance. In this study, a docetaxel-resistant cell subline (231-TR) was established from the human TNBC cell line MDA-MB-231. Both the parental and resistant cell lines exhibited similar sensitivity to the small molecule functional inhibitor of HuR, KH-3. Docetaxel and KH-3 combination therapy synergistically inhibited cell proliferation in TNBC cells and tumor growth in three animal models. KH-3 downregulated the expression levels of HuR targets (e.g., β-Catenin and BCL2) in a time- and dose-dependent manner. Moreover, KH-3 restored docetaxel's effects on activating Caspase-3 and cleaving PARP in 231-TR cells, induced apoptotic cell death, and caused S-phase cell cycle arrest. Together, our findings suggest that HuR is a critical mediator of docetaxel resistance and provide a rationale for combining HuR inhibitors and chemotherapeutic agents to enhance chemotherapy efficacy.","journal":"Molecular Oncology","year":2023,"id":337380,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":564256,"name":"Qi Zhang","orcid":"0000-0002-5824-2534","position":1,"is_corresponding":false},{"id":274868,"name":"Cuncong Zhong","orcid":"0000-0002-8777-082X","position":2,"is_corresponding":false},{"id":1060855,"name":"Lily He","orcid":"0000-0003-0023-9022","position":3,"is_corresponding":false},{"id":284309,"name":"Yuxia Zhang","orcid":"0000-0001-9951-3583","position":4,"is_corresponding":false},{"id":1069235,"name":"Ahlam M. Armaly","orcid":null,"position":5,"is_corresponding":false},{"id":274876,"name":"Jeffrey Aubé","orcid":"0000-0003-1049-5767","position":6,"is_corresponding":false},{"id":274873,"name":"Danny R. Welch","orcid":"0000-0002-1951-4947","position":7,"is_corresponding":false},{"id":274877,"name":"Liang Xu","orcid":"0000-0001-9196-4232","position":8,"is_corresponding":false},{"id":274865,"name":"Xiaoqing Wu","orcid":"0000-0003-2076-4107","position":9,"is_corresponding":false},{"id":274869,"name":"Lanjing Wei","orcid":"0000-0001-9170-0931","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:10:26.690308Z","pmid":"37357618","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":[]}