Long Noncoding RNA OIP5-AS1 Promotes Cell Apoptosis and Cataract Formation by Blocking POLG Expression Under Oxidative Stress
Invest Ophthalmol Vis Sci
; 61(12): 3, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-33006594
ABSTRACT
Purpose:
Cataract, a clouding of the intraocular lens, is the leading cause of blindness. The lens-expressed long noncoding RNA OIP5-AS1 was upregulated in lens epithelial cells from patients with cataracts, suggesting its pathogenic role in cataracts. We investigated the regulatory role of OIP5-AS1 in the development of cataracts as well as potential RNA binding proteins, downstream target genes, and upstream transcription factors.Methods:
Clinical capsules and ex vivo and in vitro cataract models were used to test OIP5-AS1 expression. Cell apoptosis was detected using Western blots, JC-1 staining, and flow cytometry. Ribonucleoprotein immunoprecipitation-qPCR was performed to confirm the interaction of OIP5-AS1 and POLG. Chromatin immunoprecipitation-qPCR was used to determine the binding of TFAP2A and the OIP5-AS1 promoter region.Results:
OIP5-AS1 was upregulated in cataract lenses and B3 cells under oxidative stress. OIP5-AS1 knockdown protected B3 cells from H2O2-induced apoptosis and alleviated lens opacity in the ex vivo cataract model. HuR functioned as a scaffold carrying OIP5-AS1 and POLG mRNA and mediated the decay of POLG mRNA. POLG was downregulated in the cataract lens and oxidative-stressed B3 cells, and POLG depletion decreased the mtDNA copy number and MMP, increased reactive oxygen species production, and sensitized B3 cells to oxidative stress-induced apoptosis. POLG overexpression reversed these effects. TFAP2A bound the OIP5-AS1 promoter and contributed to OIP5-AS1 expression.Conclusions:
We demonstrated that OIP5-AS1, activated by TFAP2A, contributed to cataract formation by inhibiting POLG expression mediated by HuR, thus leading to increased apoptosis of lens epithelial cells and aggravated lens opacity, suggesting that OIP5-AS1 is a potential target for cataract treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catarata
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Regulação da Expressão Gênica
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Apoptose
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RNA Longo não Codificante
/
DNA Polimerase gama
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
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Male
Idioma:
En
Revista:
Invest Ophthalmol Vis Sci
Ano de publicação:
2020
Tipo de documento:
Article