MicroRNA-93-5p participates in type 2 diabetic retinopathy through targeting Sirt1

Abstract

Objective To investigate the role of miR-93-5p in rats with type 2 diabetic retinopathy (DR) through targeting Sirt1. Methods The targeting correlation between miR-93-5p and Sirt1 was validated by dual-luciferase reporter gene assay. Type 2 diabetes mellitus (T2DM) rat models were received intravitreal injection of antagomir NC (negative control), miR-93-5p antagomir, miR-93-5p agomir and/or recombinant Sirt1, followed by observation of pathological changes in retina via HE staining. Besides, retinal vascular permeability was determined by fluorescein isothiocyanate-bovine serum albumin (FITC-BSA), while the retinal vasculature was observed through retinal trypsin digestion. Expression of miR-93-5p and Sirt1 was measured by qRT-PCR and Western blotting, while the levels of VEGF, proinflammatory cytokines and anti-oxidative indicators were determined using corresponding kits. Results MiR-93-5p could target Sirt1 as analyzed by the luciferase reporter gene assay. Rats in the T2DM group presented the up-regulation of miR-93-5p and down-regulation of Sirt1 in the retina, and miR-93-5p inhibition could up-regulate Sirt1 expression in the T2DM rats. Recombinant Sirt1 decreased retinal vascular permeability and acellular capillaries with improved pathological changes in retina from T2DM rats, which was abolished by miR-93-5p agomir. Moreover, miR-93-5p inhibition or Sirt1 overexpression decreased the levels of VEGF and proinflammatory cytokines while enhancing the activity of antioxidative indicators. However, indicators above had no significant differences between T2DM group and T2DM ? agomir ? Sirt1 group. Conclusion MiR-93-5p, via targeting Sirt1, could affect the vascular permeability and acellular capillaries and mitigate the inflammation and oxidative stress in the retinas, which may play a critical role in DR.

Interactive role of miR‐29, miR‐93, miR‐205, and VEGF in salivary adenoid cystic carcinoma

“…In a study on miR‐93 and tumor growth factor‐β‐mediated epithelial–mesenchymal transition (EMT) pathway on arising retinal pigment epithelium‐19 (ARPE‐19) cells, EMT was found to be triggered in mesenchymal ARPE‐19 to epithelial transition (Fuchs et al, 2020 ). Moreover, a study on Type 2 diabetic retinopathy using qRT‐PCR and Western blot analysis demonstrated that while increasing the activity of antioxidative indicators, miR‐93‐5p inhibition downregulated VEGF levels and proinflammatory cytokines via Sirt1 overexpression, possibly through YAP/HIF1a/VEGFA pathway (H. Wang et al, 2021 ). MiR‐93 in glioma cell lines and glioma tissues was significantly upregulated, and it is correlated with clinicopathologic grading and survival in patients and may directly activate PI3K/Akt signaling by suppressing PTEN, PHLPP2, and FOXO3 expression targeting 3′‐untranslated regions (UTRs) (Jiang et al, 2015b ).…”

Advances in Research Related to MicroRNA for Diabetic Retinopathy

“…Wang et al [ 156 ] identified a targeting relationship between miR-93–5p and SIRT1 using luciferase reporter gene assay. They found that miR-93–5p is upregulated and SIRT1 is downregulated in rats with DR.…”

Oxidative Stress and Its Regulation in Diabetic Retinopathy

“…An investigation of the antioxidant activity of 25-hydroxyvitamin D3 (vitamin D) in human retinal endothelial cells revealed a reduction in miR-93 transcript with high glucose and vitamin D treatment, compared to high glucose alone, as well as reduced ROS production, malondialdehyde (MDA) content, and an increased level of reduced glutathione (GSH) [ 169 ]. Another investigation using a rat model of streptozotocin-induced diabetes indicated that miR-93 targeted sirtuin 1 (SIRT1) in the diabetic retina, inducing changes indicative of oxidative stress and inflammation which could be reversed by SIRT1 overexpression [ 170 ]. Several other miRNAs have recently been implicated in oxidative damage in diabetic retinopathy, including miR-1, miR-19a, and miR-320a repression of mitochondrial SIRT transcripts SIRT3, SIRT4, and SIRT5, respectively [ 171 ], miR-301a-3p regulation of six-transmembrane epithelial antigen of prostate 4 (STEAP4) expression [ 172 ], and miR-338-3p negative regulation of glutamine transporter SLC1A5 expression, leading to ferroptosis [ 173 ].…”