{"doi":"10.17615/6956-rx80","title":"An RNA-binding protein, hu-antigen r, in pancreatic cancer epithelial to mesenchymal transition, metastasis, and cancer stem cells","abstract":"Pancreatic cancer has poor prognosis and treatment outcomes due to its highly metastatic nature and resistance to current treatments. The RNA-binding protein (RBP) Hu-antigen R (HuR) is a central player in posttranscriptional regulation of cancer-related gene expression, and contributes to tumorigenesis, tumor growth, metastasis, and drug resistance. HuR has been suggested to regulate pancreatic cancer epithelial-to-mesenchymal transition (EMT), but the mechanism was not well understood. Here, we further elucidated the role HuR plays in pancreatic cancer cell EMT, and developed a novel inhibitor specifically interrupting HuR–RNA binding. The data showed that HuR binds to the 30-UTR of the mRNA of the transcription factor Snail, resulting in stabilization of Snail mRNA and enhanced Snail protein expression, thus promoted EMT, metastasis, and formation of stem-like cancer cells (CSC) in pancreatic cancer cells. siRNA silencing or CRISPR/Cas9 gene deletion of HuR inhibited pancreatic cancer cell EMT, migration, invasion, and inhibited CSCs. HuR knockout cells had dampened tumorigenicity in immunocompromised mice. A novel compound KH-3 interrupted HuR–RNA binding, and KH-3 inhibited pancreatic cancer cell viability, EMT, migration/invasion in vitro. KH-3 showed HuR-dependent activity and inhibited HuR-positive tumor growth and metastasis in vivo.","journal":"UNC Libraries","year":2022,"id":294619,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439974,"name":"R. Ramesh","orcid":"0000-0003-2471-7746","position":1,"is_corresponding":false},{"id":979970,"name":"L. Xu","orcid":"0000-0003-0069-8501","position":2,"is_corresponding":false},{"id":976202,"name":"D.A. Dixon","orcid":null,"position":3,"is_corresponding":false},{"id":132564,"name":"P. Chen","orcid":null,"position":4,"is_corresponding":false},{"id":10639,"name":"T. Wang","orcid":"0000-0002-1152-2221","position":5,"is_corresponding":false},{"id":10720,"name":"X. Wu","orcid":"0000-0001-7655-389X","position":6,"is_corresponding":false},{"id":980295,"name":"K. Polireddy","orcid":null,"position":7,"is_corresponding":false},{"id":202028,"name":"Q. Chen","orcid":null,"position":8,"is_corresponding":false},{"id":980296,"name":"R. Dong","orcid":null,"position":9,"is_corresponding":false},{"id":548965,"name":"J. Aube","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:31:01.450041Z","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":[]}