Aberrant Expression of Long Noncoding RNAs in Early Diabetic Retinopathy
Aberrant Expression of Long Noncoding RNAs in Early Diabetic Retinopathy
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早期糖尿病视网膜病变中长非编码RNA的异常表达
DOI：
10.1167/iovs.13-13221
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发表时间：
2014-02-01
影响因子：
4.4
通讯作者：
Jiang, Qin
中科院分区：
文献类型：
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作者：
Yan, Biao;Tao, Zhi-Fu;Jiang, Qin
目的。长非编码 RNA (lncRNA) 广泛归类为长度超过 200 个核苷酸的转录本。 lncRNA介导的生物学与多种细胞过程和人类疾病有关。糖尿病视网膜病变（DR）是导致失明的主要原因之一。然而，人们对 lncRNA 在 DR 中的作用知之甚少。本研究的目的旨在鉴定参与早期 DR 的 lncRNA 并表征它们在 DR 发病机制中的作用。我们建立了链脲佐菌素 (STZ) 诱导的糖尿病小鼠模型，并使用微阵列分析对视网膜进行 lncRNA 表达谱分析。基于Pearson相关分析，构建lncRNA/mRNA共表达网络。对lncRNA共表达的mRNA进行基因本体（GO）富集和KEGG分析，以确定相关的生物学模块和病理通路。实时荧光定量PCR检测临床样本和高血糖RF/6A细胞模型中lncRNA的表达模式。结果。早期 DR 视网膜中大约有 303 个 lncRNA 异常表达，其中包括 214 个下调的 lncRNA 和 89 个上调的 lncRNA。 GO分析表明，这些lncRNA共表达的mRNA针对眼睛发育过程（本体：生物过程）、膜的组成部分（本体：细胞成分）和结构分子活性（本体：分子功能）。通路分析表明，lncRNAs共表达的mRNA主要富集于轴突引导信号通路。此外，MALAT1（一种保守的 lncRNA）在高血糖 RF/6A 细胞模型、房水样本和糖尿病患者的纤维血管膜中显着上调。结论。 lncRNA通过调节多种发病途径参与DR的发病机制。 MALAT1是一种保守的lncRNA，可能成为DR预后、诊断和治疗的潜在治疗靶点。
PURPOSE. Long noncoding RNAs (lncRNAs) are broadly classified as transcripts longer than 200 nucleotides. lncRNA-mediated biology has been implicated in a variety of cellular processes and human diseases. Diabetic retinopathy (DR) is one of the leading causes of blindness. However, little is known about the role of lncRNAs in DR The goal of this study aimed to identify lncRNAs involved in early DR and characterize their roles in DR pathogenesis.METHODS. We established a mouse model of streptozotocin (STZ)-induced diabetes, and performed lncRNA expression profiling of retinas using microarray analysis. Based on the Pearson correlation analysis, an lncRNA/mRNA coexpression network was constructed. Gene ontology (GO) enrichment and KEGG analysis of lncRNAs-coexpressed mRNAs was conducted to identify the related biological modules and pathologic pathways. Real-time PCR was conducted to detect the expression pattern of lncRNA in the clinical samples and the RF/6A cell model of hyperglycemia.RESULTS. Approximately 303 lncRNAs were aberrantly expressed in the retinas of early DR, including 214 downregulated lncRNAs and 89 upregulated lncRNAs. GO analysis indicated that these lncRNAs-coexpressed mRNAs were targeted to eye development process (ontology: biological process), integral to membrane (ontology: cellular component), and structural molecule activity (ontology: molecular function). Pathway analysis indicated that lncRNAs-coexpressed mRNAs were mostly enriched in axon guidance signaling pathway. In addition, MALAT1, a conserved lncRNA, was significantly upregulated in an RF/6A cell model of hyperglycemia, in the aqueous humor samples, and in fibrovascular membranes of diabetic patients.CONCLUSIONS. lncRNAs are involved in the pathogenesis of DR through the modulation of multiple pathogenetic pathways. MALAT1, a conserved lncRNA, may become a potential therapeutic target for the prognosis, diagnosis, and treatment of DR.