{"doi":"10.1073/pnas.2220334120","title":"Zinc treatment reverses and anti-Zn-regulated miRs suppress esophageal carcinomas in vivo","abstract":"Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% decrease in ESCC incidence vs. Zn-untreated controls. Zn treatment eliminated ESCCs by affecting a spectrum of biological processes that included downregulation of expression of the two miRs and miR-31-controlled inflammatory pathway, stimulation of miR-21-PDCD4 axis apoptosis, and reversal of the ESCC metabolome: with decrease in putrescine, increase in glucose, accompanied by downregulation of metabolite enzymes ODC and HK2. Thus, Zn treatment or miR-31/21 silencing are effective therapeutic strategies for ESCC in this rodent model and should be examined in the human counterpart exhibiting the same biological processes.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":341060,"datarank":0.6236207173780428,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.20773240904207557,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.20773240904207557,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":15,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"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":496826,"name":"Kay Huebner","orcid":null,"position":1,"is_corresponding":false},{"id":496825,"name":"Ruiyan Jing","orcid":null,"position":2,"is_corresponding":false},{"id":496157,"name":"Karl J. Smalley","orcid":"0000-0003-1502-6759","position":3,"is_corresponding":false},{"id":385342,"name":"Christopher R. Brydges","orcid":"0000-0001-5901-638X","position":4,"is_corresponding":false},{"id":6363,"name":"Oliver Fiehn","orcid":"0000-0002-6261-8928","position":5,"is_corresponding":false},{"id":496827,"name":"John L. Farber","orcid":null,"position":6,"is_corresponding":false},{"id":247626,"name":"Carlo M. Croce","orcid":"0000-0003-3788-1457","position":7,"is_corresponding":false},{"id":375700,"name":"Louise Y.Y. Fong","orcid":"0000-0001-7654-7035","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:03.393978Z","pmid":"37155893","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":[]}