{"doi":"10.3390/cancers14215273","title":"miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC","abstract":"Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and β-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC.","journal":"Cancers","year":2022,"id":263639,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"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":323107,"name":"Duo‐Yao Cao","orcid":"0000-0002-0455-4655","position":1,"is_corresponding":false},{"id":620364,"name":"Tahir B. Dar","orcid":"0000-0001-5191-8346","position":2,"is_corresponding":false},{"id":685233,"name":"Faizan Ahmed","orcid":"0000-0002-0953-2201","position":3,"is_corresponding":false},{"id":920667,"name":"Shabir Ahmad Bhat","orcid":"0000-0001-7172-8187","position":4,"is_corresponding":false},{"id":323109,"name":"Luciana C. Veiras","orcid":"0000-0002-4635-7772","position":5,"is_corresponding":false},{"id":323110,"name":"Ellen A. Bernstein","orcid":"0000-0003-3597-9653","position":6,"is_corresponding":false},{"id":920668,"name":"Abdul Arif Khan","orcid":"0000-0002-8748-1841","position":7,"is_corresponding":false},{"id":921226,"name":"Manita Chaum","orcid":null,"position":8,"is_corresponding":false},{"id":620361,"name":"Stephen L. Shiao","orcid":"0000-0001-7586-2885","position":9,"is_corresponding":false},{"id":343605,"name":"Warren G. Tourtellotte","orcid":null,"position":10,"is_corresponding":false},{"id":323111,"name":"Jorge F. Giani","orcid":"0000-0003-0481-6595","position":11,"is_corresponding":false},{"id":323112,"name":"Kenneth E. Bernstein","orcid":"0000-0001-5435-8663","position":12,"is_corresponding":false},{"id":241094,"name":"Xiaojiang Cui","orcid":"0000-0002-6843-736X","position":13,"is_corresponding":false},{"id":920669,"name":"Eric Vail","orcid":"0000-0002-6578-178X","position":14,"is_corresponding":false},{"id":323113,"name":"Zakir Khan","orcid":"0000-0002-7944-491X","position":15,"is_corresponding":false},{"id":920666,"name":"Tomohiro Shibata","orcid":"0000-0002-8766-4250","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:26:33.413850Z","pmid":"36358691","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":[]}