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小 RNA 测序揭示视网膜新生血管化中转移 RNA 衍生的小 RNA 表达谱。

Small RNA Sequencing Reveals Transfer RNA-derived Small RNA Expression Profiles in Retinal Neovascularization.

机构信息

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan 410011, China.

出版信息

Int J Med Sci. 2020 Jul 6;17(12):1713-1722. doi: 10.7150/ijms.46209. eCollection 2020.

DOI:10.7150/ijms.46209
PMID:32714074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7378657/
Abstract

Retinal neovascularization (RNV) is characterized in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and retinal vein occlusion (RVO), which leads to severe vision loss and even blindness. To reveal the altered transfer RNA-derived small RNA (tsRNA)s in RNV, and to investigate the underlying mechanisms of the altered tsRNAs involved in RNV, we carried out a small RNA sequencing to profile tsRNA expressions in the retinas of mice with oxygen-induced retinopathy (OIR) and control mice. A total of 45 tsRNAs were significantly changed (fold change ≥ 1.5 and < 0.05) in the retinas of OIR mice compared with controls. Validation by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in four selected tsRNAs was consistent with the results of small RNA sequencing. Bioinformatics analyses identified 153 altered target genes of the four validated tsRNAs. These altered target genes were largely enriched in developmental process, cell periphery and protein binding, as well as Th1 and Th2 cell differentiation pathway. Our study suggests tsRNAs play key roles in the pathogenesis of RNV, indicating their therapeutic potential to treat patients with RNV. Moreover, small RNA sequencing is a useful tool to identify changes in tsRNA expression, an important indicator of the progress of retinal diseases.

摘要

视网膜新生血管(RNV)的特征在于早产儿视网膜病变(ROP)、糖尿病性视网膜病变(DR)和视网膜静脉阻塞(RVO),这会导致严重的视力丧失,甚至失明。为了揭示 RNV 中改变的转移 RNA 衍生的小 RNA(tsRNA),并研究涉及 RNV 的改变的 tsRNA 的潜在机制,我们对氧诱导的视网膜病变(OIR)小鼠和对照小鼠的视网膜进行了小 RNA 测序,以描绘 tsRNA 的表达谱。与对照组相比,OIR 小鼠的视网膜中有 45 种 tsRNA 明显改变(倍数变化≥1.5且<0.05)。通过对四个选定的 tsRNA 进行定量实时逆转录聚合酶链反应(qRT-PCR)验证,与小 RNA 测序的结果一致。生物信息学分析鉴定了四个经验证的 tsRNA 的 153 个改变的靶基因。这些改变的靶基因主要富集在发育过程、细胞外围和蛋白质结合,以及 Th1 和 Th2 细胞分化途径中。我们的研究表明,tsRNA 在 RNV 的发病机制中发挥着关键作用,表明它们具有治疗 RNV 患者的潜力。此外,小 RNA 测序是识别 tsRNA 表达变化的有用工具,tsRNA 表达变化是视网膜疾病进展的重要指标。

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