miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway

Abstract

Introduction Diabetic retinopathy (DR) is one of the major leading causes for vision loss globally. Current study illustrates the role of miR-7a in DR. Material and Methods Retinal pericytes (RPs) and Endothelial cells (ECs) were isolated from mouse model of DR. qRT-PCR was done for expression of miR-7a and target gene mRNA, Western blot for protein expression. Identification of miR-7a target gene was done by TargetScan and Luciferase assay. Cell viability and invasion was done by MTT and Transwell chamber assay. Results The expression of miR-7a was down-regulated whereas level of IRS-2 was unregulated in isolated RPs and ECs. Luciferase assay suggested correlation between miR-7a and IRS-2, over-expression of miR-7a using a mimic resulted in suppression in viability and invasion capacity of RPs and ECs and inhibited the protein levels of PI3K/Akt cascade and IRS-2, and however the inhibitor reversed them respectively. Transfection of siRNA targeting IRS-2 caused alteration in miR-7a mediated changes in ECs suggesting that miR-7a may decrease angiogenesis in DR by inhibiting the levels of IRS-2. Conclusion miR-7a suppresses PI3K/Akt cascade via targeting IRS-2, thus decreasing the viability and invasion capacity of RPs and ECs, suggesting an interesting treatment target for DR.

Retraction: MicroRNA-330 Is an Oncogenic Factor in Glioblastoma Cells by Regulating SH3GL2 Gene

“…The following panels in Fig 5 in [ 1 ] appear similar to the following panels in [ 2 ] when rotated 180°: ○ The Mock panel in Fig 5A in [ 1 ] and the EC mimic control panel in Fig 3D in [ 2 ]. ○ The Pre-miR-con panel in Fig 5A in [ 1 ] and the EC inhibitor control panel in Fig 3D in [ 2 ]. ○ The Pre-miR-330 panel in Fig 5A in [ 1 ] and the EC miR-7a inhibitor panel in Fig 3D in [ 2 ].…”

Identification of Potential Molecular Targets and Active Ingredients of Mingmu Dihuang Pill for the Treatment of Diabetic Retinopathy Based on Network Pharmacology

“…Following activation, AKT may mediate multiple downstream target proteins, such as mediating cell growth and proliferation through phosphorylation of mTOR and mediating cell apoptosis through suppressing bad expression [ 46 ]. It has been found that activation of the PI3K/AKT signaling is involved in the pathophysiology of diabetic retinopathy and promotes the proliferation and migration of retinal endothelial cells [ 47 ]. These data demonstrate that the targets of Mingmu Dihuang pill actions identified by network pharmacology for diabetic retinopathy are in agreement with previous reports.…”

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

“…Moreover, their findings indicated that the introduction of siRNA directed against IRS-2 led to modifications in the changes facilitated by miR-7a in ECs, implying a potential role for miR-7a in diminishing angiogenesis in DR through the inhibition of IRS-2 levels. In this manner, miR-7a exerts inhibition on the PI3K/Akt signaling pathway by specifically targeting IRS-2, and subsequently led to diminished viability and reduced invasive potential in RPs and ECs [ 69 ].…”