Exosomal circular RNA circ_0074673 regulates the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells via the microRNA-1200/MEOX2 axis

Abstract

Circular RNAs (circRNAs) are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to investigate the roles and molecular mechanism underlying the effects of circ_0074673 in GDM. Exosomal morphology was visualized by transmission electron microscopy (TEM), while exosomal size and concentration were determined by nanoparticle tracking analysis (NTA). The expression of CD9 and CD63 was measured by western blotting. The levels of circ_0074673, miR-1200 and mesenchyme homeobox 2 (MEOX2) were determined by quantitative real-time polymerase chain reaction (qPCR). Cellular proliferation, migration, and angiogenesis were measured by Cell Counting Kit-8 (CCK-8), transwell, and tube formation assays, respectively. The binding relationship between circ_0074673 or MEOX2 and miR-1200 was evaluated by luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNApull-down assay. The results showed that exosomal size and concentration were greater in the umbilical cord blood of patients with GDM than in that of the healthy controls. The expression of circ_0074673 was upregulated in exosomes from GDM and in human umbilical vein endothelial cells (HUVECs) co-cultured with exosomes. High glucose (HG) treatment suppressed cellular proliferation, migration, and angiogenesis. Circ_0074673 knockdown enhanced the proliferation, migration, and angiogenesis of HG treated HUVECs (HG-HUVECs). As circ_0074673 and MEOX2 directly bind to miR-1200, circ_0074673 silencing promoted the biological functions of HG-HUVECs by sponging miR-1200 and further targeting MEOX2. Altogether, the loss of exosomal circ_0074673 facilitated the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200/MEOX2 axis, suggesting that circ_0074673 is a potential therapeutic target for GDM.

Exosomal Circular RNA hsa_circ_0046060 of Umbilical Cord Mesenchymal Stromal Cell Ameliorates Glucose Metabolism and Insulin Resistance in Gestational Diabetes Mellitus via the miR-338-3p/G6PC2 Axis

“…HUMSC-EXOs regulates the membrane translocation of glucose transporter-4 (GLUT4) and the activation of enzymes implicated in glucose metabolism to improve glucose uptake and glycogen deposit. In addition, an in vitro study on the roles of human umbilical vein endothelial cells-derived exosomal circNRA demonstrated that the expression of circ_0074673 was upregulated in exosomes isolated from GDM patients and in human umbilical vein endothelial cells incubated with exosomes [ 36 ]. Notably, the knockdown of circ_0074673 alleviates the suppression of proliferation, migration, and angiogenesis of umbilical vein endothelial cells by directly sponging miR-1200 to target MEOX2.…”

Circular RNAs in diabetes mellitus and its complications

“…Additionally, exosomal circ_0074673 is increased in the exosomes from GDM patients and in human umbilical vein endothelial cells (HUVECs) cocultured with the exosomes. Silencing circ_0074673 promotes the proliferation, migration, and angiogenesis of HG-HUVECs via the miR-1200−MEOX2 axis ( 62 ). In summary, a drug that maintains normal function of the cells by regulating circRNA expression levels may open new avenues for GDM therapy.…”

The Landscape of Exosome-Derived Non-Coding RNA in Leukemia

“…Currently, the understanding of the role of exosomal circRNA in the molecular mechanisms and possible clinical applications in leukemia are very limited and need further study. It has been extensively verified in solid tumors that exosomal circRNAs participate in numerous cancer biological processes including tumorigenesis, proliferation, angiogenesis, metastasis, drug resistance, etc ( Liu et al, 2020 ; Xie et al, 2020 ; Xu J. et al, 2020 ; Huang et al, 2021 ). Xie et al (2020) reported that exosomal circSHKBP1 regulated the miR-582-3p/HUR/VEGF pathway, suppressed HSP90 degradation, and promoted GC progression.…”