Abstract
Oxidized low-density lipoprotein (ox-LDL) is a significant risk factor for various brain vascular diseases. Circular RNA (circRNA) is involved in the pathogenesis of brain vascular diseases. This study revealed the roles of circ_CHFR in ox-LDL-mediated cell proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT). Our results showed that circ_CHFR and EGFR expressions were dramatically upregulated, while miR-15a-5p expression was downregulated in ox-LDL-induced human brain microvessel endothelial cells (HBMECs) relative to control groups. circ_CHFR knockdown hindered the effects of ox-LDL exposure on cell proliferation, cell cycle, apoptosis, and EndoMT in HBMECs, whereas these impacts were abolished by miR-15a-5p inhibitor. In addition, circ_CHFR functioned as a sponge of miR-15a-5p and miR-15a-5p bound to EGFR. Thus, we concluded that circ_CHFR silencing hindered ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through sponging miR-15a-5p in HBMECs. Our findings provide a new mechanism for studying circRNA-directed therapy in ox-LDL-induced human brain vascular diseases.
Highlights
Endothelial cells are vital cells in regulating the function and the structure of vessels [1]
The protein expression of Bcl-2 was upregulated, and the protein expression of Bax, cleaved poly (ADP-ribose) polymerase (PARP), COL1A2, and ACTA2 was downregulated by miR-15a-5p after Oxidized low-density lipoprotein (ox-LDL) treatment, but enforced Epidermal growth factor receptor (EGFR) expression abolished these effects (Figure 6g and h). These results indicated that miR-15a-5p promoted cell proliferation and repressed cell apoptosis and endothelial-to-mesenchymal transition (EndoMT) by binding to EGFR in ox-LDL-induced human brain microvessel endothelial cells (HBMECs)
Ox-LDL is harmful to many cells, including endothelial cells, and commonly induces endothelial cell injury [27]
Summary
Endothelial cells are vital cells in regulating the function and the structure of vessels [1]. CircRNA was disclosed to regulate ox-LDL-induced deleterious effects in endothelial cells. Li et al proved that circ_0003575 modulated ox-LDL-induced cell proliferation and angiogenesis in endothelial cells [15]. There are no data on regulating ox-LDL-induced human brain microvessel endothelial cells (HBMECs) injury by circ_CHFR. Fu et al explained that EGFR facilitated the invasion of BMEC via recruiting actinin-4 [22] These pieces of evidence demonstrate that EGFR may play a vital part in HBMEC development. The expression profiles of circ_CHFR, miR15a-5p, and EGFR were determined in ox-LDL-induced HBMECs. In addition, the effects of ox-LDL treatment on the proliferation, apoptosis, and endothelial-to-mesenchymal transition (EndoMT) were disclosed. Rescue experiments were employed to illustrate that circ_ CHFR knockdown regulated ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by downregulating EGFR expression through binding to miR-15a-5p
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