Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.
Profiling of circular RNAs in age-related cataract reveals circZNF292 as an antioxidant by sponging miR-23b-3p.
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DOI：
10.18632/aging.103683
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发表时间：
2020-09-10
期刊：
影响因子：
--
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Liang S;Dou S;Li W;Huang Y
白内障是世界范围内视力损害和可逆性盲的主要原因之一。越来越多的证据表明，环状RNA（circRNA）参与了多种眼部疾病的调控过程。然而，ARC中circRNA的表达谱、调控作用和潜在机制在很大程度上仍不清楚。在此，我们对来自正常和ARC晶状体的前透镜囊的circRNA进行深度测序，并检测到23，787个候选circRNA。其中，466个显著差异表达，并且与上调的相比，观察到ARC和糖尿病性白内障之间的下调circRNA的相关性更高。随后的生物信息学分析显示，某些差异表达的circRNA参与了ARC中氧化应激和凋亡相关的信号通路。值得注意的是，ARC中circZNF 292的水平显著降低，而miR-23 b-3 p显著增加。靶区预测和双荧光素酶报告基因分析证明，circZNF 292作为一种竞争性内源性RNA，通过与miR-23 b-3 p竞争来调控抗氧化基因的表达。我们的研究结果表明，ARC患者前透镜囊中表达下调的circRNA circZNF 292可能通过海绵状miR-23 b-3 p参与透镜上皮细胞抗氧化损伤和凋亡，为ARC的预防和治疗提供了潜在的靶点。
Age-related cataract (ARC) is one of the major causes of visual impairment and reversible blindness worldwide. Accumulating evidence has revealed that circular RNAs (circRNAs) are involved in multiple regulatory processes in various ocular diseases. However, the expression profile, regulatory roles, and underlying mechanisms of circRNAs in ARC remain largely unknown. Herein we deep-sequenced circRNAs of anterior lens capsules from normal and ARC lenses, and detected 23,787 candidate circRNAs. Of these, 466 were significantly differentially expressed, and a higher correlation in down-regulated circRNAs between ARC and diabetic cataract was observed compared with up-regulated ones. Subsequent bioinformatics analysis disclosed that certain differentially expressed circRNAs participated in oxidative stress and apoptosis-related signaling pathways in ARC. Notably, the level of circZNF292 was significantly decreased, while miR-23b-3p was significantly increased in ARC. The target region prediction and dual-luciferase reporter assays proved that circZNF292 acted as a competitive endogenous RNA to regulate the expression of anti-oxidative genes through competing with miR-23b-3p. Our results indicate that circZNF292, a down-regulated circRNA in the anterior lens capsule of ARC patients, may be involved in resistance to oxidative damage and apoptosis of lens epithelial cells by sponging miR-23b-3p, providing a potential target for prevention and treatment of ARC.
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影响因子：
17.8
作者：
Kandarakis, Stylianos A.;Piperi, Christina;Papavassiliou, Athanasios G.
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