{"doi":"10.1101/2020.07.01.182766","title":"HYPERGLYCEMIA-INDUCED MIR-467 DRIVES TUMOR INFLAMMATION AND GROWTH IN BREAST CANCER","abstract":"ABSTRACT Tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. Hyperglycemic patients have a higher risk of developing breast cancer (BC). We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth ( P <.001). Tumors from hyperglycemic mice had a 2-fold increase in macrophage accumulation compared to normoglycemic controls ( P <.001), and TAM infiltration was prevented by the miR-467 antagonist ( P <.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs normoglycemic patients (2.17-fold, P =.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold inc., P =.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients ( P <.001) and increased 56-fold in adjacent normal tissue ( P =.008). Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125127,"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":0.9446,"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":571765,"name":"Irene Krukovets","orcid":null,"position":1,"is_corresponding":false},{"id":570830,"name":"Santoshi Muppala","orcid":"0000-0001-7830-9591","position":2,"is_corresponding":false},{"id":570831,"name":"Dmitriy Verbovetskiy","orcid":"0000-0002-3828-4200","position":3,"is_corresponding":false},{"id":526848,"name":"Jessica Zhang","orcid":"0000-0002-4801-6509","position":4,"is_corresponding":false},{"id":571766,"name":"Olga Stenina‐Adognravi","orcid":null,"position":5,"is_corresponding":false},{"id":571764,"name":"Jasmine Gajeton","orcid":null,"position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-18T23:15:15.482227Z","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":[]}