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阿霉素诱导的大鼠 lncRNAs 表达揭示了 lncRNAs 在慢性肾小球肾炎发病机制中的潜在作用。

LncRNAs expression in adriamycin-induced rats reveals the potential role of LncRNAs contributing to chronic glomerulonephritis pathogenesis.

机构信息

Department of Pharmacy, The first Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, China.

Department of Pharmacy, The first Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Hefei, China.

出版信息

Gene. 2019 Mar 1;687:90-98. doi: 10.1016/j.gene.2018.11.050. Epub 2018 Nov 17.

Abstract

BACKGROUND

Chronic glomerulonephritis (CGN) is the most common form of primary glomerular disease with unclear molecular mechanisms. Currently, limited study on long non-coding RNAs (lncRNAs) in CGN is available. Our study aimed to identify potential lncRNAs and genes in the normal and adriamycin-induced CGN rats, which to explore the potential molecular mechanisms of CGN pathogenesis.

METHODS

To identify LncRNAs specifically expressed in CGN, the expression of LncRNAs in glomerular tissues of rats from the adriamycin-induced group (n = 3) was compared with that in the control group (n = 3) using RNA-sequencing and real-time polymerase chain reaction (RT-PCR). Identification of differentially expressed lncRNAs and mRNAs were performed between the 2 groups. Gene ontology (GO) and pathway enrichment analyses were performed to analyze the biological functions and pathways for the differentially expressed mRNAs. LncRNA-mRNA co-expression network was constructed to analyses for the genes. The protein-protein interaction (PPI) network was visualized.

RESULTS

A total of 114 significantly up-regulated and 86 down-regulated lncRNAs, 1038 up-regulated and 88 down-regulated mRNAs were identified. Additionally, Il6, with the highest connectivity degree in PPI network, was noteworthy enriched in various kinds pathways. Coding-non-coding gene co-expression networks (CNC network) were drawn based on the correlation analysis between the differentially expressed LncRNAs and mRNAs. Ten LncRNAs, NONRATT000964.2, NONRATT018086.2, NONRATT023684.2, NONRATT009530.2, NONRATT006315.2, NONRATT026805.2, MSTRG.9260.1, NONRATT009155.2, MSTRG.7681.1, NONRATT009275.2, were selected to analyze the relationship between LncRNAs and CGN via the CNC network and GO analysis. Real-time PCR result confirmed that the six LncRNAs were specifically expressed in the CGN rats.

CONCLUSIONS

The ten LncRNAs were differentially expressed and might play important roles in the development of CGN. Key genes, such as Il6, Ptprc, TOP2a, Fos, Myc, etc., may be crucial biomarkers for CGN.

摘要

背景

慢性肾小球肾炎(CGN)是最常见的原发性肾小球疾病,其分子机制尚不清楚。目前,关于 CGN 中长非编码 RNA(lncRNA)的研究有限。本研究旨在鉴定正常和阿霉素诱导的 CGN 大鼠中潜在的 lncRNA 和基因,以探讨 CGN 发病机制的潜在分子机制。

方法

为了鉴定 CGN 中特异性表达的 LncRNAs,使用 RNA-seq 和实时聚合酶链反应(RT-PCR)比较阿霉素诱导组(n=3)和对照组(n=3)大鼠肾小球组织中的 LncRNAs 表达。对两组之间的差异表达 lncRNA 和 mRNA 进行鉴定。对差异表达的 mRNAs 进行基因本体(GO)和通路富集分析,以分析其生物学功能和通路。构建 lncRNA-mRNA 共表达网络,以分析基因。可视化蛋白质-蛋白质相互作用(PPI)网络。

结果

共鉴定出 114 个显著上调和 86 个下调的 lncRNA,1038 个上调和 88 个下调的 mRNA。此外,PPI 网络中具有最高连接度的 Il6 显著富集在各种途径中。基于差异表达 LncRNAs 和 mRNAs 之间的相关性分析,绘制编码-非编码基因共表达网络(CNC 网络)。选择 10 个 LncRNA,NONRATT000964.2、NONRATT018086.2、NONRATT023684.2、NONRATT009530.2、NONRATT006315.2、NONRATT026805.2、MSTRG.9260.1、NONRATT009155.2、MSTRG.7681.1、NONRATT009275.2,通过 CNC 网络和 GO 分析分析 LncRNA 与 CGN 之间的关系。实时 PCR 结果证实,这 6 个 LncRNA 特异性表达在 CGN 大鼠中。

结论

这 10 个 LncRNA 差异表达,可能在 CGN 的发展中发挥重要作用。关键基因,如 Il6、Ptprc、TOP2a、Fos、Myc 等,可能是 CGN 的重要生物标志物。

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