miR-7 Reduces High Glucose Induced-damage Via HoxB3 and PI3K/AKT/mTOR Signaling Pathways in Retinal Pigment Epithelial Cells

Abstract

Background: Diabetic retinopathy (DR) is a common complication of diabetes. This study investigated the effect of miR-7 in the regulation of cell proliferation via the HoxB3 gene and PI3K/AKT/mTOR signaling pathways in DR. Methods: Human retinal pigment epithelial cell line (ARPE-19) cultured in normal medium (Control) and high glucose medium (25mM glucose, HG) was transfected with mimics NC (HG+ mimics NC), miR-7 mimics (HG+miR-7 mimics), inhibitor NC (HG+ inhibitor NC), and miR-inhibitor (HG+miR-7 inhibitor). The cells were assayed for viability, apoptosis, and expression of genes. Results: HG reduced cell viability and increased apoptosis. However, miR-7 mimics reduced the apoptosis. PCR results showed that miR-7 was significantly upregulated after transfection with miR-7 mimics. The expression of Hoxb3, mTOR, p-PI3K, and p- AKT was significantly downregulated at mRNA and protein levels after miR-7 mimics transfection, while no difference was observed for PI3K and AKT expression. Conclusions: Our findings demonstrate that miR-7 regulates the growth of retinal epithelial cells through various pathways and is a potential therapeutic target for the prevention and treatment of diabetic retinopathy.

MiR-542-5p regulates the progression of diabetic retinopathy by targeting CARM1

“…Conversely, some miRNAs have the opposite role. For instance, miR-7 has been demonstrated to inhibit apop- tosis and alleviate HG-induced damage in retinal pigment epithelial cells (Yang et al, 2019). MiR-142-5p is decreased in retinal tissues of DR rats and HG-treated human retinal endothelial cells, and improves pathological effects in retinal tissues (Liu et al, 2020).…”

CircZNF532 knockdown protects retinal pigment epithelial cells against high glucose‐induced apoptosis and pyroptosis by regulating the miR‐20b‐5p/STAT3 axis

“…Human RPE cell line ARPE-19 (ATCC, USA) was cultured in DMEM (Gibco, USA) supplemented with 10% fetal bovine serum (FBS) and maintained in an incubator (5% CO 2 ) at 37°C. The ARPE-19 cells were exposed to 5 mM [normal glucose (NG)], 10 mM, 15 mM, 20 mM, or 25 mM (HG) of glucose (Sigma-Aldrich, USA) for 72 h. The exposure of cells to high glucose (25 mM) was used to establish the cell model of diabetic retinopathy [25][26][27] . Short hairpin RNA (shRNA) for circZNF532 (sh-ZNF532), circZNF532 expression vector (oe-ZNF532), miR-20b-5p mimic, miR-20b-5p inhibitor, STAT3 expression vector (oe-STAT3), and their corresponding negative control (NC) (all by GenePharma, China) were introduced into ARPE-19 cells alone or in combination using lipofectamine 2000 reagents (Invitrogen, USA).…”

Crosstalk between MiRNAs/lncRNAs and PI3K/AKT signaling pathway in diabetes mellitus: Mechanistic and therapeutic perspectives

“…However, no discernible variation was observed in the expression of PI3K and AKT. In this manner, through the modulation of the PI3K/AKT/mTOR signaling pathways, miR-7 orchestrates the retinal epithelial cells growth, thus emerging as a promising therapeutic target for mitigating and managing DR [ 67 ]. In addition, Cao et al examined the involvement of miR-7 in the context of DR and explored its underlying mechanism.…”