Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models.
Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models.
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DOI：
10.3389/fgene.2020.556712
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发表时间：
2020
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Chen X;Zhou R;Shan K;Sun Y;Yan B;Sun X;Wang J
环状RNA是一类共价闭合的环状RNA转录物，通过海绵状作用与多种细胞过程和神经系统疾病相关。青光眼是视神经病变的一种形式，迄今尚未进行环状RNA的表达谱分析。所有形式的青光眼最常见的特征是视网膜神经节细胞的损失。虽然青光眼的发病机制尚未完全了解，但眼内压无疑是使慢性高眼压（COH）动物成为经典青光眼模型的唯一已证实的可改变因素。基于这些发现，我们完成了第一次深入研究大鼠视网膜环状RNA表达谱，以确定可能的生物标志物诊断青光眼。采用巩膜外静脉结扎法和微球注射法建立大鼠高眼压模型。总共检测到15，819个环状RNA。此外，在两种COH大鼠中鉴定了3，502个差异表达的环状RNA，其中691个上调，2，811个下调。显示了7个显著下调的（log 2FoldChange <-2.5和调整的P < 0.001）和7个显著上调的（log 2FoldChange> 2.5和调整的P < 0.001）环状RNA。鉴定了与前14个环状RNA比对的6个靶microRNA。根据环状RNA-microRNA网络的构建和circBase信息，在人类基因组中只有RNO_CIRCpedia_1775具有同源hsa_circ_0023826。hsa_circ_0023826和宿主基因TENM 4（端神经元跨膜蛋白4）的mRNA在5名青光眼患者和5名白内障对照患者的房水样品中被验证。hsa_circ_0023826在青光眼患者中的表达显著降低，而TENM 4 mRNA与白内障患者相比无显著差异（分别为P = 0.024和P = 0.294）。本研究的结果全面表征了环状RNA在青光眼影响的眼睛中的表达谱，并通过两种不同的高眼压大鼠模型进行了验证。与作为最高差异表达环状RNA基础的靶microRNA一起，在青光眼患者的房水中鉴定并进一步验证了hsa_circ_0023826及其宿主基因TENM 4的新靶点，表明该疾病的有希望的生物标志物。
Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both log2FoldChange < −2.5 and adjusted P < 0.001) and seven significantly upregulated (both log2FoldChange > 2.5 and adjusted P < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients (P = 0.024 and P = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
2.5
作者：
GOLDBERG, MP;MONYER, H;CHOI, DW
通讯作者：
CHOI, DW
CERNA假设：隐藏RNA语言的Rosetta石头？
影响因子：
64.5
作者：
Salmena L;Poliseno L;Tay Y;Kats L;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y