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RNA测序将长链非编码RNA鉴定为氧化应激下人角膜内皮功能障碍的潜在治疗靶点。

RNA-seq identifies long non-coding RNAs as potential therapeutic targets for human corneal endothelial dysfunction under oxidative stress.

作者信息

Shan Kun, Qiu Jini, Zhou Rongmei, Gu Jiayu, Zhang Xueling, Zhang Chaoran, Xiang Jun, Xu Jianjiang

机构信息

Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, China.

Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Exp Eye Res. 2021 Dec;213:108820. doi: 10.1016/j.exer.2021.108820. Epub 2021 Oct 30.

DOI:10.1016/j.exer.2021.108820
PMID:34728181
Abstract

Human corneal endothelial cells (CECs) have limited ability to regenerate in vivo. Oxidative stress has been proposed as one potential reason. Understanding the mechanism of oxidative stress-induced CEC dysfunction might provide novel targets for improving CEC regenerative capacity, and help develop non-surgical therapeutic strategies for CEC dysfunction. Long non-coding RNAs (lncRNAs) are non-coding transcripts with multiple biological functions. The roles of lncRNAs in ocular cells under oxidative stress have been widely studied, such as lens epithelial cells, trabecular meshwork cells, and retinal ganglion cells. In the current study, we established oxidative stress-induced CEC dysfunction model in vitro. By RNA sequencing technology, we identified 824 differentially expressed lncRNAs in CEC dysfunction group, including 667 upregulated lncRNAs and 157 downregulated lncRNAs. We finally demonstrated that CEC functions under oxidative stress, including cellular proliferation, apoptosis, and anti-oxidative stress ability, could be regulated by different lncRNAs, including lncRNA-Z93241.1, lncRNA-XLOC_000818, and lncRNA-AC007952.4. Targeting these lncRNAs might be useful to further elucidate the pathology of CEC dysfunction and develop novel therapeutic strategy.

摘要

人角膜内皮细胞(CECs)在体内的再生能力有限。氧化应激被认为是一个潜在原因。了解氧化应激诱导的CEC功能障碍机制可能为提高CEC再生能力提供新靶点,并有助于开发针对CEC功能障碍的非手术治疗策略。长链非编码RNA(lncRNAs)是具有多种生物学功能的非编码转录本。lncRNAs在氧化应激下眼细胞中的作用已得到广泛研究,如晶状体上皮细胞、小梁网细胞和视网膜神经节细胞。在本研究中,我们在体外建立了氧化应激诱导的CEC功能障碍模型。通过RNA测序技术,我们在CEC功能障碍组中鉴定出824个差异表达的lncRNAs,其中包括667个上调的lncRNAs和157个下调的lncRNAs。我们最终证明,氧化应激下的CEC功能,包括细胞增殖、凋亡和抗氧化应激能力,可由不同的lncRNAs调节,包括lncRNA-Z93241.1、lncRNA-XLOC_000818和lncRNA-AC007952.4。靶向这些lncRNAs可能有助于进一步阐明CEC功能障碍的病理机制并开发新的治疗策略。

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