{"doi":"10.1161/circulationaha.124.070243","title":"A Novel Hidden Protein p-414aa Encoded by\n            <i>circSETD2(14,15</i>\n            ) Inhibits Vascular Remodeling","abstract":"<jats:sec>\n            <jats:title>BACKGROUND:</jats:title>\n            <jats:p>Phenotypic switching of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia, is a fundamental cause of vascular remodeling diseases such as atherosclerosis and hypertension. Novel hidden proteins encoded by circular RNAs play crucial roles in disease progression, yet their involvement in vascular remodeling diseases has not been comprehensively studied. This study identifies a novel protein derived from a circular RNA in VSMCs and demonstrates its potential role in regulating vascular remodeling.</jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:</jats:title>\n            <jats:p>\n              Cell proliferation assays were performed to investigate the effects of\n              <jats:italic toggle=\"yes\">circSETD2(14,15</jats:italic>\n              ) on VSMC proliferation. Techniques such as vector construction, immunoprecipitation–mass spectrometry, and dual-luciferase reporter gene were used to confirm that\n              <jats:italic toggle=\"yes\">circSETD2(14,15</jats:italic>\n              ) encoded a novel protein, p-414aa. The interaction between p-414aa and HuR (human antigen R) was validated with techniques such as co-immunoprecipitation, mass spectrometry, and proximity ligation assay. Through experiments including RNA sequencing and RNA immunoprecipitation, the interaction between HuR and\n              <jats:italic toggle=\"yes\">C-FOS</jats:italic>\n              (C-Fos proto-oncogene) mRNA was revealed. The role of p-414aa in neointimal hyperplasia was assessed with a carotid artery ligation model in male mice.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:</jats:title>\n            <jats:p>\n              Overexpression of\n              <jats:italic toggle=\"yes\">circSETD2(14,15</jats:italic>\n              ) inhibits VSMC phenotypic switching. The novel protein p-414aa, encoded by\n              <jats:italic toggle=\"yes\">circSETD2(14,15</jats:italic>\n              ), interacts with HuR to reduce\n              <jats:italic toggle=\"yes\">C-FOS</jats:italic>\n              mRNA stability, thereby suppressing VSMC proliferation and ultimately inhibiting neointimal hyperplasia in male mice.\n            </jats:p>\n          </jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:</jats:title>\n            <jats:p>\n              We uncover a novel hidden protein derived from\n              <jats:italic toggle=\"yes\">circSETD2(14,15</jats:italic>\n              ), called p-414aa, that inhibits vascular remodeling.\n              <jats:italic toggle=\"yes\">CircSETD2(14,15</jats:italic>\n              ) and p-414aa may serve as potential therapeutic targets for vascular remodeling diseases.\n            </jats:p>\n          </jats:sec>","journal":"Circulation","year":2025,"id":611183,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"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":1572573,"name":"Li-Yun Yang","orcid":"0000-0001-5716-4098","position":1,"is_corresponding":false},{"id":1572574,"name":"An-Qi Zhao","orcid":null,"position":2,"is_corresponding":false},{"id":1572575,"name":"Zhao-Yi Wang","orcid":null,"position":3,"is_corresponding":false},{"id":973235,"name":"Sen Wang","orcid":"0000-0002-4409-469X","position":4,"is_corresponding":false},{"id":773403,"name":"Miao Gong","orcid":null,"position":5,"is_corresponding":false},{"id":1572576,"name":"Ming-Qi Zheng","orcid":null,"position":6,"is_corresponding":false},{"id":1479225,"name":"Gang Liu","orcid":"0000-0002-4664-5459","position":7,"is_corresponding":false},{"id":1572577,"name":"Shu-Yan Yang","orcid":"0000-0003-1525-6415","position":8,"is_corresponding":false},{"id":1572578,"name":"Jia-Jie Lin","orcid":"0000-0003-3338-6264","position":9,"is_corresponding":false},{"id":1572579,"name":"Shao-Guang Sun","orcid":"0000-0002-2827-0948","position":10,"is_corresponding":false},{"id":1572572,"name":"Si-Fan Wang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A Novel Hidden Protein p-414aa Encoded by <i>circSETD2(14,15</i> ) Inhibits Vascular Remodeling","abstract":"BACKGROUND: Phenotypic switching of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia, is a fundamental cause of vascular remodeling diseases such as atherosclerosis and hypertension. Novel hidden proteins encoded by circular RNAs play crucial roles in disease progression, yet their involvement in vascular remodeling diseases has not been comprehensively studied. This study identifies a novel protein derived from a circular RNA in VSMCs and demonstrates its potential role in regulating vascular remodeling. METHODS: Cell proliferation assays were performed to investigate the effects of circSETD2(14,15 ) on VSMC proliferation. Techniques such as vector construction, immunoprecipitation–mass spectrometry, and dual-luciferase reporter gene were used to confirm that circSETD2(14,15 ) encoded a novel protein, p-414aa. The interaction between p-414aa and HuR (human antigen R) was validated with techniques such as co-immunoprecipitation, mass spectrometry, and proximity ligation assay. Through experiments including RNA sequencing and RNA immunoprecipitation, the interaction between HuR and C-FOS (C-Fos proto-oncogene) mRNA was revealed. The role of p-414aa in neointimal hyperplasia was assessed with a carotid artery ligation model in male mice. RESULTS: Overexpression of circSETD2(14,15 ) inhibits VSMC phenotypic switching. The novel protein p-414aa, encoded by circSETD2(14,15 ), interacts with HuR to reduce C-FOS mRNA stability, thereby suppressing VSMC proliferation and ultimately inhibiting neointimal hyperplasia in male mice. CONCLUSIONS: We uncover a novel hidden protein derived from circSETD2(14,15 ), called p-414aa, that inhibits vascular remodeling. CircSETD2(14,15 ) and p-414aa may serve as potential therapeutic targets for vascular remodeling diseases.","is_dataset_classified":null,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40099364","pmcid":null,"openalex_id":"https://openalex.org/W4408577220","authors":[],"funders":[],"total_grants":0,"fwci":5.3172,"citation_percentile":0.96299888,"influential_citations":0,"citation_trend":[{"year":2025,"count":6},{"year":2026,"count":7}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://doi.org/10.1161/circulationaha.124.070243","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40099364","host_type":"repository"}],"fields_of_study":["Circular RNAs in diseases","Cancer-related molecular mechanisms research","Cardiovascular Disease and Adiposity"],"mesh_terms":["ELAV-Like Protein 1","RNA, Circular","Proto-Oncogene Mas","Animals","Cells, Cultured","Humans","Male","Mice, Inbred C57BL","Muscle, Smooth, Vascular","Proto-Oncogene Proteins c-fos","Myocytes, Smooth Muscle","Cell Proliferation","Mice","Neointima","Vascular Remodeling"],"keywords":["Vascular smooth muscle","Immunoprecipitation","Neointimal hyperplasia","Intimal hyperplasia","Medicine","Messenger RNA","Neointima","Cancer research","Cell biology","Proximity ligation assay","RNA","Vascular remodelling in the embryo","Molecular biology","Biology","Internal medicine","Gene","Immunology","Receptor","Antibody","Biochemistry","Restenosis","Hyperplasia","Vascular remodeling","Translating","myocytes, smooth muscle","Elav-like Protein 1","Rna, Circular"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-01T16:28:12.012177Z","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":[]}