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基因芯片分析显示长非编码 RNA SOX2OT 是糖尿病肾病的一个新的候选调控因子。

Microarray analysis reveals long non‑coding RNA SOX2OT as a novel candidate regulator in diabetic nephropathy.

机构信息

Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

出版信息

Mol Med Rep. 2018 Dec;18(6):5058-5068. doi: 10.3892/mmr.2018.9534. Epub 2018 Oct 4.

DOI:10.3892/mmr.2018.9534
PMID:30320339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6236268/
Abstract

Diabetic nephropathy (DN) is a highly complex syndrome involving multiple dysregulated biological processes. Long non‑coding RNAs (lncRNAs) are now believed to have an important function in various diseases. However, their roles in DN remain largely unknown. Therefore, the present study was performed in order to investigate the lncRNAs that have a crucial role in DN. db/db mice were used as a DN model while db/m mice served as a control to search for lncRNAs which may have important roles in DN. Microarray and bioinformatics analysis gave an overview of the features of differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis demonstrated the typical biological alterations in DN. A co‑expression network of lncRNAs and mRNAs revealed the complex interaction pattern in DN conditions. Further data investigation indicated that SOX2‑overlapping transcript (SOX2OT), which was significantly downregulated in DN mice, may be the potentially functional lncRNA contributing to the onset of DN. The UCSC database demonstrated that SOX2OT was highly conserved in mice and humans. Additionally further study using cultured human podocytes and mesangial cells confirmed the downregulation of SOX2OT using reverse transcription‑quantitative polymerase chain reaction and fluorescence in situ hybridization. However, the cellular location of SOX2OT depended on certain cell types. Taken together, the results of the present study indicated that SOX2OT may act as an important regulator in the pathogenesis of DN by interacting with various mRNAs with critical roles in DN.

摘要

糖尿病肾病（DN）是一种涉及多个失调生物过程的高度复杂综合征。长链非编码 RNA（lncRNA）现在被认为在各种疾病中具有重要功能。然而，它们在 DN 中的作用在很大程度上仍然未知。因此，本研究旨在探讨在 DN 中具有关键作用的 lncRNA。db/db 小鼠被用作 DN 模型，而 db/m 小鼠作为对照，以寻找可能在 DN 中具有重要作用的 lncRNA。微阵列和生物信息学分析概述了差异表达基因的特征。基因本体论和京都基因与基因组百科全书富集分析显示了 DN 中的典型生物学改变。lncRNA 和 mRNA 的共表达网络揭示了 DN 条件下的复杂相互作用模式。进一步的数据研究表明，在 DN 小鼠中显著下调的 SOX2 重叠转录物（SOX2OT）可能是潜在功能的 lncRNA，有助于 DN 的发生。UCSC 数据库表明 SOX2OT 在小鼠和人类中高度保守。此外，使用培养的人足细胞和系膜细胞的进一步研究通过逆转录-定量聚合酶链反应和荧光原位杂交证实了 SOX2OT 的下调。然而，SOX2OT 的细胞位置取决于特定的细胞类型。总之，本研究结果表明，SOX2OT 可能通过与在 DN 中具有关键作用的各种 mRNAs 相互作用，作为 DN 发病机制中的重要调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/6ee65f023b40/MMR-18-06-5058-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/5fd77010cf62/MMR-18-06-5058-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/51e15215a7ee/MMR-18-06-5058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/b564d7b5323b/MMR-18-06-5058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/54c0713f67c1/MMR-18-06-5058-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/071b507e8234/MMR-18-06-5058-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/6ee65f023b40/MMR-18-06-5058-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/5fd77010cf62/MMR-18-06-5058-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/51e15215a7ee/MMR-18-06-5058-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/b564d7b5323b/MMR-18-06-5058-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/54c0713f67c1/MMR-18-06-5058-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/071b507e8234/MMR-18-06-5058-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf60/6236268/6ee65f023b40/MMR-18-06-5058-g05.jpg

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