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Paper IPM / Biological Sciences / 17905 |
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Abstract: | |||||||||||||
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
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