{"doi":"10.1073/pnas.1920333117","title":"Abrogation of esophageal carcinoma development in miR-31 knockout rats","abstract":"MicroRNA-31 (miR-31) is overexpressed in esophageal squamous cell carcinoma (ESCC), a deadly disease associated with dietary Zn deficiency and inflammation. In a Zn deficiency-promoted rat ESCC model with miR-31 up-regulation, cancer-associated inflammation, and a high ESCC burden following N -nitrosomethylbenzylamine (NMBA) exposure, systemic antimiR-31 delivery reduced ESCC incidence from 85 to 45% ( P = 0.038) and miR-31 gene knockout abrogated development of ESCC ( P = 1 × 10 −6 ). Transcriptomics, genome sequencing, and metabolomics analyses in these Zn-deficient rats revealed the molecular basis of ESCC abrogation by miR-31 knockout. Our identification of EGLN3, a known negative regulator of nuclear factor κB (NF-κB), as a direct target of miR-31 establishes a functional link between oncomiR-31, tumor suppressor target EGLN3, and up-regulated NF-κB–controlled inflammation signaling. Interaction among oncogenic miR-31, EGLN3 down-regulation, and inflammation was also documented in human ESCCs. miR-31 deletion resulted in suppression of miR-31–associated EGLN3/NF-κB–controlled inflammatory pathways. ESCC-free, Zn-deficient miR-31 −/− rat esophagus displayed no genome instability and limited metabolic activity changes vs. the pronounced mutational burden and ESCC-associated metabolic changes of Zn-deficient wild-type rats. These results provide conclusive evidence that miR-31 expression is necessary for ESCC development.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":101352,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9609,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295060,"name":"Cristian Taccioli","orcid":"0000-0003-2995-5612","position":1,"is_corresponding":false},{"id":496824,"name":"Alexey Palamarchuk","orcid":null,"position":2,"is_corresponding":false},{"id":496156,"name":"Guidantonio Malagoli Tagliazucchi","orcid":"0000-0001-5581-4851","position":3,"is_corresponding":false},{"id":496825,"name":"Ruiyan Jing","orcid":null,"position":4,"is_corresponding":false},{"id":496157,"name":"Karl J. Smalley","orcid":"0000-0003-1502-6759","position":5,"is_corresponding":false},{"id":331807,"name":"Sili Fan","orcid":"0000-0002-3497-1695","position":6,"is_corresponding":false},{"id":496158,"name":"Joseph Altemus","orcid":"0000-0002-9954-3819","position":7,"is_corresponding":false},{"id":6363,"name":"Oliver Fiehn","orcid":"0000-0002-6261-8928","position":8,"is_corresponding":false},{"id":496826,"name":"Kay Huebner","orcid":null,"position":9,"is_corresponding":false},{"id":496827,"name":"John L. Farber","orcid":null,"position":10,"is_corresponding":false},{"id":247626,"name":"Carlo M. Croce","orcid":"0000-0003-3788-1457","position":11,"is_corresponding":false},{"id":375700,"name":"Louise Y.Y. Fong","orcid":"0000-0001-7654-7035","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T22:39:38.259162Z","pmid":"32123074","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":[]}