MiR-200c-3p regulates pyroptosis by targeting SLC30A7 in diabetic retinopathy

Abstract

Clinical relevance: MicroRNAs (miRNAs) have been reported to be involved in the progression of various diseases. Studying the regulatory mechanisms of miRNAs can help clinical treatment. Background: Diabetic retinopathy (DR) is one of the complications of diabetes. The objective of this study was to elucidate the underlying molecular mechanisms by which miR-200c-3p regulates the pyroptosis of DR cell. Methods: Human retinal microvascular endothelial cells (HRMECs) and high glucose (HG) cultures established DR cell model in vitro. RT-qPCR is used to detect the expression level of miRNAs. CCK-8 assays and flow cytometry are used to detect apoptosis of HRMECs cell. Western blotting is used to detect cleaved caspase-3, cleaved caspase-1, and N-GSDMD proteins levels in HRMECs. The ELISA assay is used to detect the expression of IL-1β and IL-18. Predict and validate potential binding sites between miR-200c-3p and SLC30A7 by dual luciferase reporter gene analysis. Results: The results showed that HG caused damage to HRMECs through the pyroptosis pathway rather than the apoptosis pathway. MiR-200c-3p is highly expressed in HG induced-HRMECs, and knockdown of miR-200c-3p mitigates HG-induced HRMECs pyroptosis. MiR-200c-3p negatively targets SLC30A7 in HRMECs, and miR-200c-3p regulates pyroptosis of HG-induced HRMECs by targeting SLC30A7. Conclusion: The results suggest that miR-200c-3p might be a promising interference target for DR prevention and treatment. The results of current study may provide new insights into development of therapeutic strategies for DR.

Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease

“…Several studies provide evidence that individual circulating miRNAs are associated with dyslipidemia and CAD [ 49 ]. In a recent study, Li et al showed that hsa-miR-200c-3p is involved in pyroptosis (a highly inflammatory programmed cell death characterized by cell rupture, nuclear formation, and high concentrations of nuclear serous fluid) by targeting SLC30A7 in patients affected by diabetic retinopathy (DR) [ 50 ]. SLC30A7 is involved in the regulation of insulin secretion and in the regulation of diabetic cardiomyopathy progression by influencing muco-mitochondrial coupling in hyperglycemic cardiomyocytes [ 51 , 52 ].…”

The role of ncRNAs‐mediated pyroptosis in diabetes and its vascular complications

“…In addition, in HG‐induced HRMEC, the overexpression of miR‐200c‐3p and low expression of SLC30A7 were observed. miR‐200c‐3p can interact with SLC30A7, and a miR‐200c‐3p inhibitor can increase the expression of SLC30A7 and reverse the pyroptosis of HRMEC caused by HG 106 . HG inhibits pyroptosis of RPE by regulating METTL3.…”

Diabetic Neuropathy of the Retina and Inflammation: Perspectives

“…Growing evidence shows that ginsenoside has significant effects in ameliorating the pathological changes of diabetes and its complications via inhibition of the pyroptosis-associated inflammasome pathway [122]. Li et al indicate that MiR-200c-3p regulated high glucose-induced pyroptosis of human retinal microvascular endothelial cells by targeting SLC03A7 [123]. Gu et al suggest that microRNA-192 represses retinal pigment epithelium cell pyroptosis induced by high glucose via regulation of the FTO-α-keratoglutarate-dependent dioxygenase/NLRP3 signaling pathway [124].…”