Crosstalk between MIR-96 and IRS/PI3K/AKT/VEGF cascade in hRPE cells; A potential target for preventing diabetic retinopathy.

Autor: Hosseinpoor Z; Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran., Soheili ZS; Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran., Davari M; Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran., Latifi-Navid H; Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.; School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran., Samiee S; Blood Transfusion Research Center High Institute for Research and Education in Transfusion Medicine, Tehran, Iran., Samiee D; Department of Computer Science, Royal Holloway University of London, Egham, Surrey, United Kingdom.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Sep 30; Vol. 19 (9), pp. e0310999. Date of Electronic Publication: 2024 Sep 30 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0310999
Abstrakt: Regulation of visual system function demands precise gene regulation. Dysregulation of miRNAs, as key regulators of gene expression in retinal cells, contributes to different eye disorders such as diabetic retinopathy (DR), macular edema, and glaucoma. MIR-96, a member of the MIR-183 cluster family, is widely expressed in the retina, and its alteration is associated with neovascular eye diseases. MIR-96 regulates protein cascades in inflammatory and insulin signaling pathways, but further investigation is required to understand its potential effects on related genes. For this purpose, we identified a series of key target genes for MIR-96 based on gene and protein interaction networks and utilized text-mining resources. To examine the MIR-96 impact on candidate gene expression, we overexpressed MIR-96 via adeno-associated virus (AAV)-based plasmids in human retinal pigment epithelial (RPE) cells. Based on Real-Time PCR results, the relative expression of the selected genes responded differently to overexpressed MIR-96. While the expression levels of IRS2, FOXO1, and ERK2 (MAPK1) were significantly decreased, the SERPINF1 gene exhibited high expression simultaneously. pAAV-delivered MIR-96 had no adverse effect on the viability of human RPE cells. The data showed that changes in insulin receptor substrate-2 (IRS2) expression play a role in disrupted retinal insulin signaling and contribute to the development of diabetic complications. Considered collectively, our findings suggest that altered MIR-96 and its impact on IRS/PI3K/AKT/VEGF axis regulation contribute to DR progression. Therefore, further investigation of the IRS/PI3K/AKT/VEGF axis is recommended as a potential target for DR treatment.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Hosseinpoor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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