RETRACTED ARTICLE: Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

Abstract

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 TGFβR2 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 TGFβR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3′ untranslated region (UTR) of TGFβR2. 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.

Circular RNA circ_0010283 regulates the viability and migration of oxidized low‑density lipoprotein‑induced vascular smooth muscle cells via an miR‑370‑3p/HMGB1 axis in atherosclerosis

“…These results suggested that circ_0010283 may regulate the progression of atherosclerosis by sponging miR-370-3p. In addition, the inhibitory role of miR-370-3p in atherosclerosis progression was observed, which was consistent with previous studies (19,32).…”

“…For example, Zhang et al (16) have demonstrated that miR-370-3p is associated with acute pneumonia, and Hou et al (17) have reported that miR-370-3p suppresses VSMc viability in cerebral aneurysm. In addition, circ_0003204 can directly target miR-370-3p to repress the progression of atherosclerosis (32). In the present study, miR-370-3p was downregulated in ox-LdL-induced VSMcs compared with non-induced cells, and was negatively modulated by circ_0010283.…”

<p>Plasmatic circRNA Predicting the Occurrence of Human Glioblastoma</p>

“…13 Increasing evidence has indicated that circRNAs play a crucial role including carcinogenesis, progression and clinical outcomes of various human cancers. 14,15 For example, researchers have found that circEPSTI1 could promote cell proliferation and apoptosis through sponging miR-4753 and miR-6809 to regulate the BCL11A level in triple-negative breast cancer. 16 The circNT5E could function as a sponge for the miR-422a, which is involved in cell proliferation, migration, and invasion in GBM.…”

CircRNAs open a new era in the study of cardiovascular disease (Review)

“…It is understood that circRNAs are involved in numerous pathological mechanisms underlying cVds, such as AS, immune response, apoptosis, cell proliferation, autophagy, cell senescence and myocardial repair (103)(104)(105)(106)(107)(108)(109). Emerging evidence has suggested that circRNAs play an important role in the occurrence and development of cVd (110).…”