PMID- 31900142 OWN - NLM STAT- MEDLINE DCOM- 20200605 LR - 20211108 IS - 1423-0127 (Electronic) IS - 1021-7770 (Print) IS - 1021-7770 (Linking) VI - 27 IP - 1 DP - 2020 Jan 3 TI - Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFbetaR2/phosph-SMAD3 axis. PG - 11 LID - 10.1186/s12929-019-0595-9 [doi] LID - 11 AB - BACKGROUND: Circular RNAs (circRNAs) represent a class of non-coding RNAs (ncRNAs) which are widely expressed in mammals and tissue-specific, of which some could act as critical regulators in the atherogenesis of cerebrovascular disease. However, the underlying mechanisms by which circRNA regulates the ectopic phenotype of endothelial cells (ECs) in atherosclerosis remain largely elusive. METHODS: CCK-8, transwell, wound healing and Matrigel assays were used to assess cell viability, migration and tube formation. QRT-qPCR and Immunoblotting were used to examine targeted gene expression in different groups. The binding sites of miR-370-3p (miR-370) with TGFbetaR2 or hsa_circ_0003204 (circ_0003204) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The localization of circ_0003204 and miR-370 in ECs were investigated by fluorescence in situ hybridization (FISH). Gene function and pathways were enriched through Metascape and gene set enrichment analysis (GSEA). The association of circ_0003204 and miR-370 in extracellular vesicles (EVs) with clinical characteristics of patients were investigated using multiple statistical analysis. RESULTS: Circ_0003204, mainly located in the cytoplasm of human aorta endothelial cells (HAECs), was upregulated in the ox-LDL-induced HAECs. Functionally, the ectopic expression of circ_0003204 inhibited proliferation, migration and tube formation of HAECs exposed to ox-LDL. Mechanically, circ_0003204 could promote protein expression of TGFbetaR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3' untranslated region (UTR) of TGFbetaR2. Furthermore, the expression of circ_0003204 in plasma EVs was upregulated in the patients with cerebral atherosclerosis, and represented a potential biomarker for diangnosis and prognosis of cerebrovascular atherogenesis. CONCLUSIONS: Circ_0003204 could act as a novel stimulator for ectopic endothelial inactivation in atherosclerosis and a potential biomarker for cerebral atherosclerosis. FAU - Zhang, Shanchao AU - Zhang S AUID- ORCID: 0000-0002-5543-4530 AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. zhangshanchao2012@163.com. FAU - Song, Guixiang AU - Song G AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Yuan, Jing AU - Yuan J AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Qiao, Shan AU - Qiao S AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Xu, Shan AU - Xu S AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Si, Zhihua AU - Si Z AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Yang, Yang AU - Yang Y AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Xu, Xuxu AU - Xu X AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. FAU - Wang, Aihua AU - Wang A AD - Department of Neurology, the First Affiliated Hospital of Shandong, First Medical University, NO.16766 JingShi Road, Jinan, 250014, Shandong, China. LA - eng GR - No.ZR2016HP04, No.ZR2019MH062/Natural Science Foundation of Shandong Province/ GR - No.81601020/National Natural Science Foundation of China/ PT - Journal Article PT - Retracted Publication DEP - 20200103 PL - England TA - J Biomed Sci JT - Journal of biomedical science JID - 9421567 RN - 0 (MIRN370 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - 0 (SMAD3 protein, human) RN - 0 (Smad3 Protein) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II) RN - EC 2.7.11.30 (TGFBR2 protein, human) SB - IM RIN - J Biomed Sci. 2021 Oct 12;28(1):71. PMID: 34641858 MH - Atherosclerosis/*genetics/pathology MH - Binding Sites/genetics MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Cell Survival/genetics MH - Endothelial Cells/metabolism/pathology MH - Gene Expression Regulation/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - MicroRNAs/*genetics MH - Protein Binding/genetics MH - RNA, Circular/*genetics MH - Receptor, Transforming Growth Factor-beta Type II/*genetics MH - Signal Transduction/genetics MH - Smad3 Protein/*genetics PMC - PMC6941276 OTO - NOTNLM OT - Atherosclerosis OT - Endothelial cell OT - Hsa_circ_0003204 OT - MiR-370-3p OT - TGFbetaR2 COIS- The authors declare that they have no competing interests. EDAT- 2020/01/05 06:00 MHDA- 2020/06/06 06:00 PMCR- 2020/01/03 CRDT- 2020/01/05 06:00 PHST- 2019/07/21 00:00 [received] PHST- 2019/11/18 00:00 [accepted] PHST- 2020/01/05 06:00 [entrez] PHST- 2020/01/05 06:00 [pubmed] PHST- 2020/06/06 06:00 [medline] PHST- 2020/01/03 00:00 [pmc-release] AID - 10.1186/s12929-019-0595-9 [pii] AID - 595 [pii] AID - 10.1186/s12929-019-0595-9 [doi] PST - epublish SO - J Biomed Sci. 2020 Jan 3;27(1):11. doi: 10.1186/s12929-019-0595-9.