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

Small RNA Sequencing Reveals Transfer RNA-derived Small RNA Expression Profiles in Retinal Neovascularization
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小 RNA 测序揭示了视网膜新生血管中转移 RNA 衍生的小 RNA 表达谱。

DOI:
10.7150/ijms.46209
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发表时间:
2020-01-01
影响因子:
3.6
通讯作者:
Zhou, Yedi
Zhou, Yedi
中科院分区:
医学4区
文献类型:
--
作者:
Peng, Yingqian;Zou, Jingling;Zhou, Yedi

文献摘要

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视网膜新生血管(RNV)以早产儿视网膜病变(ROP)、糖尿病视网膜病变(DR)和视网膜静脉阻塞(RVO)为特征,导致严重的视力丧失甚至失明。为了揭示RNV中改变的转移核糖核糖核酸衍生的小RNA(TsRNA)S,并探讨参与RNV的改变的tsRNA的潜在机制,我们进行了小RNA测序,分析了氧诱导视网膜病变(OIR)小鼠和对照组小鼠视网膜中tsRNA的表达。与对照组相比,OIR组小鼠视网膜中共有45个tsRNAs发生了显著改变(折叠式改变=1.5,P<0.05)。通过实时定量逆转录聚合酶链式反应(qRT-PCR)对4个tsRNAs进行验证,结果与小RNA测序结果一致。生物信息学分析确定了四个有效tsRNAs中153个改变的靶基因。这些改变的靶基因在发育过程、细胞外周和蛋白结合以及Th1和Th2细胞分化途径中都有很大程度的丰富。我们的研究表明tsRNAs在RNV的发病机制中起着关键作用,表明它们有治疗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表达是视网膜疾病进展的重要指标。
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 P < 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.