<p>Interference of Hsa_circ_0003928 Alleviates High Glucose-Induced Cell Apoptosis and Inflammation in HK-2 Cells via miR-151-3p/Anxa2</p>

Abstract

Background Diabetic nephropathy (DN) is a severe end-stage kidney disease developed from diabetes mellitus. The involvement of circular RNA (circRNAs) in the regulation of DN pathogenesis has been implied, but the underlying mechanism of DN is still lacking. This study aimed to investigate the effect of hsa_circ_0003928 on the inflammation and apoptosis of high glucose (HG)-induced renal tubular cells. Methods The expression of hsa_circ_0003928, miR-151-3p and Anxa2 in blood samples from DN patients and healthy controls was detected by RT-qPCR. Human renal epithelial cells HK-2 were incubated with D-glucose (30 mmol/l) to establish DN model in vitro. RT-qPCR analysis confirmed the transfection effects and detected the expressions of TNF-α, IL-6 and IL-1β. Western blotting analysis determined the protein expression of Anxa2, Bcl-2, Bax, cleaved caspase-3 and caspase-3. The production of ROS was detected by DCF-DA method and production of inflammatory cytokines was verified by ELISA assay. CCK-8 assay and TUNEL assay were performed to determine cell viability and apoptosis, respectively. Dual-luciferase reporter assay was performed to confirm the relationship between miR-151-3p and hsa_circ_0003928 or Anxa2. Results Hsa_circ_0003928 and Anxa2 mRNA levels were increased, whereas miR-151-3p was decreased in both HG-induced HK-2 cells and patients with DN. Hsa_circ_0003928 knockdown could decrease cell viability loss and apoptosis, increase Bcl-2 expression, and decrease Bax and cleaved caspase-3 expression. Besides, hsa_circ_0003928 knockdown suppressed HG-induced overproduction of ROS, TNF-α, IL-6 and IL-1β. However, the effects made by miR-151-3p inhibition were opposite to those made by hsa_circ_0003928 knockdown. Furthermore, the binding sites between miR-151-3p and hsa_circ_0003928 or Anxa2 were predicted and verified. Protein expression of Anxa2 was suppressed by hsa_circ_0003928 knockdown, which was rescued by miR-151-3p inhibition. Conclusion These results demonstrated that hsa_circ_0003928 could act as a sponge of miR-151-3p and regulate HG-induced inflammation and apoptosis partly through regulating Anxa2.

Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox‐LDL‐induced endothelial dysfunction in atherosclerosis by functioning as a miR‐876‐3p sponge

“…Circ_0035266 upregulation accentuated the inflammatory response in human bronchial epithelial cells 29 . Hsa_circ_0003928 mitigated the high glucose‐induced cell apoptosis and inflammation in diabetic nephropathy 30 . In this study, circ_0093887 expression was downregulated in AS patients and ox‐LDL‐treated HAECs.…”

Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

“…Our study determined that Atg5 was signi cantly downregulated during VSMC calci cation both in vitro and in vivo. In addition, there were several targets of miR-151-3p have been identi ed such as Anxa2 (35), NRAS(36), and tumor protein p53 (37). This study focused on the regulation of miR151-3p and Atg5 in VSMC calci cation, other potential regulatory axis should be explored in the subsequent experiments.…”

Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

“…Though current data was mainly derived from MCs, circRNAs may also play a role in other kidney cell types, such as tubular epithelial cells (TECs) and podocytes. The expression of several circRNAs, including hsa_circ_0003928, circ_WBSCR17, circACTR2, and circEIF4G2, were shown to be increased by HG stimulation in TECs model ( 96 – 99 ). Interference of hsa_circ_0003928 alleviated HG-induced secretion of inflammatory cytokines and repressed apoptosis in TECs by sponging miR-151-3p partly through regulating Anxa2, suggesting this circRNAs could positively modulate inflammation and apoptosis ( 96 ).…”

“…The expression of several circRNAs, including hsa_circ_0003928, circ_WBSCR17, circACTR2, and circEIF4G2, were shown to be increased by HG stimulation in TECs model ( 96 – 99 ). Interference of hsa_circ_0003928 alleviated HG-induced secretion of inflammatory cytokines and repressed apoptosis in TECs by sponging miR-151-3p partly through regulating Anxa2, suggesting this circRNAs could positively modulate inflammation and apoptosis ( 96 ). Circ_WBSCR17 aggravated HG-induced inflammatory responses and fibrosis in HK-2 cells by activating SOX6 via targeting miR-185-5p ( 97 ).…”