Chen Sheng, Dong Chenglong, Qian Xiaoxiao, Huang Shanshan, Feng Yamin, Ye Xiaolong, Miao Heng, You Qiang, Lu Yibing, Ding Dafa
Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210000,China; Nanjing Medical University, Nanjing, 210029, China.
Department of Endocrinology, Yancheng First People's Hospital, Yancheng, 224006, China.
J Diabetes Complications. 2017 Mar;31(3):569-576. doi: 10.1016/j.jdiacomp.2016.11.017. Epub 2016 Dec 8.
Long noncoding RNAs (lncRNAs) are implicated in various biological processes and human diseases. Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). We explored the potential functions of lncRNAs in DN.
We established a mouse model of DN and compared lncRNA expression patterns between DN model and db/m control mouse kidney tissues using microarray analysis. lncRNA function was predicted by gene ontology enrichment and KEGG pathway analyses of lncRNAs-coexpressed mRNAs. Quantitative reverse-transcription PCR was used for validation. Cis- and trans-regulation analyses were conducted to reveal potential relationships between lncRNAs and their target genes.
In DN, 311 lncRNAs were dysregulated. LncRNA-coexpressed mRNAs were mainly targeted to golgi apparatus (ontology: cellular component), catalytic activity (ontology: molecular function), and mitotic nuclear division (ontology: biological process), and were mostly enriched in glutathione metabolism signaling. One hundred forty-seven lncRNAs were regarded as cis-regulatory. Several groups of lncRNAs may participate in biological pathways related to DN via trans-regulation of protein-coding genes.
Hundreds of lncRNAs are dysregulated in DN. These lncRNAs might be involved in the pathogenesis of DN by modulating multiple molecular pathways. Our findings provide potential candidate biomarkers for predicting or diagnosing DN.
长链非编码RNA（lncRNAs）参与多种生物学过程及人类疾病。糖尿病肾病（DN）是终末期肾病（ESRD）的主要病因。我们探究了lncRNAs在DN中的潜在功能。
我们建立了DN小鼠模型，并使用微阵列分析比较了DN模型与db/m对照小鼠肾组织之间的lncRNA表达模式。通过对与lncRNAs共表达的mRNA进行基因本体富集分析和KEGG通路分析来预测lncRNA功能。采用定量逆转录PCR进行验证。进行顺式和反式调控分析以揭示lncRNAs与其靶基因之间的潜在关系。
在DN中，311种lncRNAs表达失调。与lncRNAs共表达的mRNA主要靶向高尔基体（本体：细胞成分）、催化活性（本体：分子功能）和有丝分裂核分裂（本体：生物学过程），并且大多富集于谷胱甘肽代谢信号通路。147种lncRNAs被视为顺式调控。几组lncRNAs可能通过对蛋白质编码基因的反式调控参与与DN相关的生物学途径。
在DN中有数百种lncRNAs表达失调。这些lncRNAs可能通过调节多种分子途径参与DN的发病机制。我们的发现为预测或诊断DN提供了潜在的候选生物标志物。
