{"doi":"10.20944/preprints202405.1098.v1","title":"MEG3-Mediated Oral Squamous Cell Carcinoma-Derived Exosomal miR-421 Activates Angiogenesis by Targeting HS2ST1 in Vascular Endothelial Cells","abstract":"Exosomal microRNAs (miRNAs) from cancer cells play a key role in mediating the oral squamous cell carcinoma (OSCC) microenvironment. The objective aimed to investigate how long non-coding RNA (lncRNA) MEG3 affects OSCC angiogenesis through exosomal miR-421. Global miRNA microarray analysis and quantitative real-time PCR (qRT-PCR) were performed to determine the level of miRNAs in OSCC cells-derived exosomes. Cell migration, invasion, tube formation, immunohistochemistry and hemoglobin concentration were used to study the effects of exosomal miR-421 in angiogenesis. Western blotting was used to determine the expression level of HS2ST1 and VEGFR2-related downstream proteins. MiRNA array and qRT-PCR identified upregulation of miR-421 in OSCC cell-derived exosomes. Furthermore, exosome-miR-421 can be taken up by human umbilical vein endothelial cells (HUVEC) and then targets HS2ST1 through VEGF-mediated ERK and AKT phosphorylation, thereby promoting HUVEC migration, invasion, and tube formation. Additionally, enforced expression of lncRNA MEG3 in OSCC cells reduced exosomal miR-421 levels and then increased HS2ST1 expression, thereby reducing the VEGF/VEGFR2 pathway in HUVEC. Our results demonstrate a novel mechanism by which lncRNA MEG3 can act as a tumor suppressor and regulate endothelial angiogenesis through the exosomal miR-421/HS2ST1 axis, which provides a potential therapeutic strategy for OSCC angiogenesis.","journal":"Preprints.org","year":2024,"id":488508,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"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":0.9608,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1229010,"name":"Sung-Tau Chou","orcid":null,"position":1,"is_corresponding":false},{"id":1228560,"name":"Yuan-Ming Hsu","orcid":"0000-0002-6876-8492","position":2,"is_corresponding":false},{"id":1229011,"name":"Wan-Ju Chao","orcid":null,"position":3,"is_corresponding":false},{"id":1229012,"name":"Guan-Hsun Wu","orcid":null,"position":4,"is_corresponding":false},{"id":1229013,"name":"Jenn-Ren Hsiao","orcid":null,"position":5,"is_corresponding":false},{"id":70289,"name":"Horng‐Dar Wang","orcid":"0000-0001-9570-3611","position":6,"is_corresponding":false},{"id":1228561,"name":"Shine‐Gwo Shiah","orcid":"0000-0002-1003-973X","position":7,"is_corresponding":false},{"id":1229009,"name":"Chia-Yun Huang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:19.655720Z","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":[]}