{"doi":"10.3389/fphar.2021.614044","title":"MiR-19a-3p Suppresses M1 Macrophage Polarization by Inhibiting STAT1/IRF1 Pathway","abstract":"<jats:p>Macrophages, an important type of immune cells, are generally polarized to classically activated macrophage (M1) or alternatively activated macrophage (M2) to respond to environmental stimuli. Signal transducer and activator of transcription 1 (STAT1), a very important transcription factor, can promote M1 macrophage polarization. However, the mechanisms of regulating STAT1 in macrophage polarization remain unclear. In the present study, STAT1 was markedly elevated, however, miR-19a-3p was down-regulated in interferon (IFN)-γ and lipopolysaccharide (LPS) treated RAW264.7 cells, and dual-luciferase reporter assay identified that miR-19a-3p directly targeted STAT1 by binding to its 3′UTR. Up-regulated miR-19a-3p inhibited M1 polarization by targeting STAT1/interferon regulatory factor 1 (IRF1) and vice versa <jats:italic>in vitro</jats:italic>. Consistently, overexpression of miR-19a-3p in LPS treated mice by systemically administering agomiR-19a-3p effectively reduced the inflammation in mouse lung tissues, and inhibited M1 macrophage polarization via suppressing STAT1/IRF1 pathway. In summary, our study confirmed that miR-19a-3p, as a direct regulator of STAT1, inhibited M1 macrophages polarization. The miR-19a-3p/STAT1/IRF1 pathway can potentially be used to design novel immunotherapy for modulating macrophage polarization.</jats:p>","journal":"Frontiers in Pharmacology","year":2021,"id":686013,"datarank":0.5926865577872142,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"self_citation_contribution":0.5926865577872142,"citation_network_contribution":0.0,"self_endowment_contribution":0.5926865577872142,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":956057,"name":"Qiang Guo","orcid":"0000-0003-3520-5439","position":1,"is_corresponding":false},{"id":537864,"name":"Jing Zou","orcid":"0009-0005-1714-0776","position":2,"is_corresponding":false},{"id":246792,"name":"Bin Wang","orcid":"0000-0001-6036-5579","position":3,"is_corresponding":false},{"id":567065,"name":"Zhen Zhang","orcid":"0000-0002-1840-3110","position":4,"is_corresponding":false},{"id":1383748,"name":"Ran Wei","orcid":"0000-0001-9147-6327","position":5,"is_corresponding":false},{"id":231847,"name":"Lin Zhao","orcid":"0000-0002-8865-859X","position":6,"is_corresponding":false},{"id":1792297,"name":"Yunhong Zhang","orcid":null,"position":7,"is_corresponding":false},{"id":971260,"name":"Chu Chu","orcid":"0000-0003-2938-7862","position":8,"is_corresponding":false},{"id":1792298,"name":"Xiaoxiao Fu","orcid":null,"position":9,"is_corresponding":false},{"id":1346263,"name":"Xia Li","orcid":"0000-0003-1328-9061","position":10,"is_corresponding":false},{"id":1735679,"name":"Xiaoxiao Zhu","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"MiR-19a-3p Suppresses M1 Macrophage Polarization by Inhibiting STAT1/IRF1 Pathway","abstract":"<jats:p>Macrophages, an important type of immune cells, are generally polarized to classically activated macrophage (M1) or alternatively activated macrophage (M2) to respond to environmental stimuli. Signal transducer and activator of transcription 1 (STAT1), a very important transcription factor, can promote M1 macrophage polarization. However, the mechanisms of regulating STAT1 in macrophage polarization remain unclear. In the present study, STAT1 was markedly elevated, however, miR-19a-3p was down-regulated in interferon (IFN)-γ and lipopolysaccharide (LPS) treated RAW264.7 cells, and dual-luciferase reporter assay identified that miR-19a-3p directly targeted STAT1 by binding to its 3′UTR. Up-regulated miR-19a-3p inhibited M1 polarization by targeting STAT1/interferon regulatory factor 1 (IRF1) and vice versa <jats:italic>in vitro</jats:italic>. Consistently, overexpression of miR-19a-3p in LPS treated mice by systemically administering agomiR-19a-3p effectively reduced the inflammation in mouse lung tissues, and inhibited M1 macrophage polarization via suppressing STAT1/IRF1 pathway. In summary, our study confirmed that miR-19a-3p, as a direct regulator of STAT1, inhibited M1 macrophages polarization. The miR-19a-3p/STAT1/IRF1 pathway can potentially be used to design novel immunotherapy for modulating macrophage polarization.</jats:p>","is_dataset_classified":null,"base_score":3.9512437185814275,"endowment":3.9512437185814275,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34017248","pmcid":"PMC8129022","openalex_id":"https://openalex.org/W3158672620","authors":[],"funders":[],"total_grants":0,"fwci":2.3435,"citation_percentile":0.89433696,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":13},{"year":2023,"count":7},{"year":2024,"count":11},{"year":2025,"count":14},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2021.614044/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2021.614044/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fphar.2021.614044/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fphar.2021.614044","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34017248","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8129022","host_type":"repository"},{"url":"https://doaj.org/article/8bd95176d4954b4d9ab60adc18e0a0a6","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8129022","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8129022?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Immune cells in cancer","Immune Cell Function and Interaction","Phagocytosis and Immune Regulation"],"mesh_terms":[],"keywords":["STAT1","Macrophage polarization","IRF1","STAT protein","Cell biology","IRF5","Chemistry","M2 Macrophage","Lipopolysaccharide","Immune system","Macrophage","Biology","Regulator","Cancer research","Transcription factor","Innate immune system","Signal transduction","In vitro","Interferon regulatory factors","STAT3","Immunology","Biochemistry","Post-transcriptional regulation","M1 Macrophage","Mir-19a-3p"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T18:20:03.283178Z","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":[]}