Liang Shuqi, Dou Shengqian, Li Wenfeng, Huang Yusen
Medical College of Qingdao University, Qingdao, China.
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Qingdao, China.
Aging (Albany NY). 2020 Sep 10;12(17):17271-17287. doi: 10.18632/aging.103683.
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.
年龄相关性白内障(ARC)是全球视力损害和可逆转失明的主要原因之一。越来越多的证据表明,环状RNA(circRNA)参与多种眼部疾病的多个调控过程。然而,circRNA在ARC中的表达谱、调控作用及潜在机制仍 largely未知。在此,我们对正常晶状体和ARC晶状体的前囊膜circRNA进行了深度测序,检测到23787个候选circRNA。其中,466个有显著差异表达,与上调的circRNA相比,ARC与糖尿病性白内障之间下调的circRNA具有更高的相关性。随后的生物信息学分析表明,某些差异表达的circRNA参与了ARC中的氧化应激和凋亡相关信号通路。值得注意的是,circZNF292水平在ARC中显著降低,而miR-23b-3p显著升高。靶区域预测和双荧光素酶报告基因实验证明,circZNF292作为竞争性内源RNA,通过与miR-23b-3p竞争来调节抗氧化基因的表达。我们的结果表明,circZNF292是ARC患者前囊膜中下调的circRNA,可能通过海绵化miR-23b-3p参与晶状体上皮细胞对氧化损伤和凋亡的抵抗,为ARC的防治提供了一个潜在靶点。