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MiR ‐1246 promotes anti‐apoptotic effect of mini‐αA in oxidative stress‐induced apoptosis in retinal pigment epithelial cells
Author(s) -
Chen Qianyin,
Lin Huimin,
Deng Xuan,
Li Shengnan,
Zhang Jinglin
Publication year - 2020
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/ceo.13751
Subject(s) - apoptosis , oxidative stress , macular degeneration , microbiology and biotechnology , retinal , medicine , chemistry , biology , biochemistry , ophthalmology
Background Geographic atrophy (GA) is a late‐stage symptom of an age‐related macular degeneration (AMD), characterized by the loss of retinal pigment epithelial (RPE) cells and photoreceptor functions. Despite being a major cause of blindness in individuals of 65 years of age and older, some forms of AMD, including GA, still lack targeted treatment. Our previous study demonstrated that mini‐αA peptide, which contains the functional site of αA‐crystallin, protected RPE cells from NaIO 3 ‐induced apoptosis. Methods To further investigate the underlying mechanism, we applied next‐generation sequencing analysis to identify miR‐1246 as a putative mediator of mini‐αA protective function. To investigate the role of miR‐1246 in RPE cell apoptosis, a stable miR‐1246‐low‐expression cell line was established by using miR‐1246 inhibitor. A 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was used to investigate the proliferation of RPE cells, mRNA and miR‐1246 expression were detected by the quantitative reverse transcriptase‐polymerase chain reaction. Results We have further identified caspase‐3 and caspase‐14 as molecular targets of miR‐1246 involved in regulation of apoptosis in NaIO 3 ‐incubated cells. Interestingly, disruption of miR‐1246 expression enhanced anti‐apoptotic effect of mini‐αA on RPE cells during oxidative stress. Conclusions Our results provide a mechanistic basis for evaluation of miR‐1246 as a new candidate target for the clinical treatment of AMD.