Circ_0093887 regulated ox-LDL induced human aortic endothelial cells viability, apoptosis, and inflammation through modulating miR-758-3p/BAMBI axis in atherosclerosis

Abstract

BACKGROUND: Compelling evidence demonstrated that circular RNAs (circRNAs) were involved in the progression of atherosclerosis (AS). However, the role of circ_0093887 in the progression of AS is unclear. The purpose of this study was to explore the role and mechanism of circ_0093887 in oxidized-low density lipoprotein (ox-LDL)-induced human aortic endothelial cells (HAECs). METHODS: HAECs were stimulated by ox-LDL to simulate AS-like injury in vitro. Circ_0093887, microRNA-758-3p (miR-758-3p), and BMP And Activin Membrane-Bound Inhibitor (BAMBI) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). PCNA, Bax, Bcl-2, and BAMBI protein levels were detected by western blot. Cell viability and apoptosis were examined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Tube formation assay was used to assess tube formation. The levels of inflammatory factors TNF-α and IL-1β were detected by corresponding ELISA kits. The relationship between miR-758-3p and circ_0093887 or BAMBI was tested via dual-luciferase reporter analysis and RNA immunoprecipitation. Oxidative stress related indexes (ROS and MDA) were detected by corresponding kits. RESULTS: The expression levels of circ_0093887 and BAMBI were prominently downregulated in ox-LDL-induced HAECs compared with control, whereas the expression of miR-758-3p was upregulated. Overexpression of circ_0093887 promoted HAECs viability and tube formation, and restrained cell apoptosis in ox-LDL-induced HAECs compared with untreated HAECs. Mechanistically, circ_0093887 regulated the expression of BAMBI through miR-758-3p. Further experiments showed that upregulation of miR-758-3p reversed changes in cell function induced by circ_0093887. In addition, reduced BAMBI salvaged miR-758-3p knockdown mediated effects on cell function. CONCLUSION: Circ_0093887 demonstrated its diagnostic and therapeutic value in AS by promoting the role of the miR-758-3p/BAMBI axis in the ox-LDL-induced endothelial injury of HAECs.

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis

“…MiR-497-5p helps regulate genes, and we found ox-LDL affects it mostly through oxidative stress, triggering pathways like NF-κB and MAPK that change miRNA levels, including miR-497-5p [ 24 , 25 ]. However, ox-LDL's effect on miR-497-5p might also involve lipid changes or other stress pathways [ 26 , 27 ], showing the complex ways ox-LDL and miR-497-5p interact in endothelial cells, with oxidative stress being a key but not the only factor.…”

miR-758-3p/ILK signaling modulated angiogenesis by regulating VEGFA in wound healing

“…MiR-758-3p has been shown to play an important role in regulating cell proliferation, migration and invasion in many kinds of tumors 25 , 26 . Moreover, miR-758-3p has been found to inhibit cell viability and tube formation in aortic endothelial cells 27 . Considering the therapeutic value of miR-758-3p and its function of targeting ILK, we used miR-758-3p to treat mice with wounds.…”

CircLZIC regulates ox-LDL-induced HUVEC cell proliferation and apoptosis via Micro-330-5p/NOTCH2 axis in atherosclerosis

“…These circRNAs include circRNA-PTPRA [ 13 ], circSCRG1 [ 14 ], and circ_0026218 [ 15 ] and so on. For example, circ_0093887 can regulate ox-LDL induced human aortic endothelial cells viability, apoptosis, and inflammation through modulating miR-758-3p/BAMBI axis in AS [ 16 ]. Circ_CHMP5 aggravates ox-LDL induced damage to human umbilical vein endothelial cells through miR-516b-5p/TGFßR2 axis [ 17 ].…”