miR-7a Targets Insulin Receptor Substrate-2 Gene and Suppresses Viability and Invasion of Cells in Diabetic Retinopathy Mice via PI3K-Akt-VEGF Pathway
Authors Ji Z, Luo J, Su T, Chen C, Su Y
Received 24 November 2020
Accepted for publication 11 January 2021
Published 16 February 2021 Volume 2021:14 Pages 719—728
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Juei-Tang Cheng
Zhenyu Ji,1 Jinyuan Luo,1 Ting Su,2 Changzheng Chen,1 Yu Su1
1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China; 2Eye Institute of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, People’s Republic of China
Correspondence: Yu Su
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China
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.
Keywords: miR-7a, diabetic retinopathy; DR, IRS-2, PI3K/Akt, endothelial cells; ECs, retinal pericytes; RPs
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