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MiR-181a-5p may regulate cell proliferation and autophagy in myopia and the associated retinopathy
Bo Jiang1, Nan Hong1, Liyue Zhang1
1Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
Abstract:
The mechanism of myopia and the associated retinopathy remains unclear, and dysregulated microRNAs (miRNAs) are implicated in this disease. In this research, we purposed to find out the regulatory function that miRNAs play in myopia and the associated retinopathy. We first performed miRNA microarray analysis in a lens-induced myopia mouse model and found that miR-9-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-181a-5p were elevated in the myopic retina. Then, we examined the functions and regulatory mechanisms of miR-181a-5p utilizing the human retinal pigment epithelium (RPE) cell line ARPE-19 by overexpressing miR-181a-5p. RNA sequencing (RNA-Seq) and qRT-PCR analysis were employed to identify differentially expressed genes after transfection. The qRT‒PCR outcomes, immunoblotting, and immunofluorescence indicated that the SGSH expression was significantly hindered through miR-181a-5p overexpression. MiR-181a-5p overexpression has the ability to elevate RPE cell proliferation and induce autophagy by targeting SGSH. We validated the negative influence of miR-181a-5p on the SGSH expression through luciferase reporter assays, which demonstrated its ability to target the 3' untranslated region of SGSH. The reversal of implications of miR-181a-5p overexpression was achieved through SGSH upregulation. We provided novel perspectives into the miR-181a-5p function in regulating myopia development and may serve as a target for therapy and molecular biomarker for myopia.
Insights
MicroRNAs (miRNAs) are involved in myopia. This study found that miR-181a-5p targets SGSH, promoting retinal pigment epithelium cell proliferation and autophagy, offering potential therapeutic targets for myopia.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- The mechanisms of myopia and associated retinopathy are not fully understood.
- Dysregulated microRNAs (miRNAs) are implicated in the pathogenesis of myopia.
Purpose of the Study:
- To investigate the regulatory role of miRNAs in myopia and associated retinopathy.
- To elucidate the function and mechanism of miR-181a-5p in myopia development.
Main Methods:
- MiRNA microarray analysis in a mouse model of lens-induced myopia.
- Overexpression of miR-181a-5p in human retinal pigment epithelium (RPE) cells (ARPE-19).
- RNA sequencing (RNA-Seq), qRT-PCR, immunoblotting, immunofluorescence, and luciferase reporter assays.
Main Results:
- Several miRNAs, including miR-181a-5p, were elevated in the myopic retina.
- miR-181a-5p overexpression hindered SGSH expression in RPE cells.
- miR-181a-5p promoted RPE cell proliferation and induced autophagy by targeting SGSH.
- SGSH upregulation reversed the effects of miR-181a-5p overexpression.
Conclusions:
- miR-181a-5p plays a significant role in regulating myopia development by targeting SGSH.
- miR-181a-5p may serve as a potential therapeutic target and molecular biomarker for myopia.
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