Identification of miRNA-Target Gene-Transcription Factor Regulatory Network as Functional Motifs Involved in Glomerular Diabetic Nephropathy

IF 0.6 4区生物学 Q4 GENETICS & HEREDITY Russian Journal of Genetics Pub Date : 2024-06-19 DOI:10.1134/s1022795424700261

Gh. Nuoroozi, E. Zareie, M. Yarizadeh, P. Ghadermarzi, H. Zali, Z. Molavi

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Abstract

The gene regulatory approach based on retrieving information from the database provides a detailed characterization of the molecular mechanisms of disease progression at the level of miRNAs, Transcription Factors (TFs), and genes. Moreover, gene regulatory networks can find an interaction between the miRNAs, TFs, and genes involved in diabetic nephropathy (DN), but the underlying mechanisms of motif remain unclear. We first gathered genes related to glomeruli diabetic nephropathy from GEO and CTD database. Besides, miRNAs targeting genes were collected from the public databases and GEO. Furthermore, regulator TFs were accumulated from related public databases. After that, we explored the regulatory relationships between TF-miRNA, miRNA-Gene, TF-Gene, and miRNA–TF using FANMOD software. Finally, a gene regulatory network consisting of miRNAs, genes, and TFs was constructed, helping the Cytoscape. The global const parameter in FANMOD software used to discover the interaction between miRNAs, genes, TFs, and 3-node regulatory motif types were detected in the resulting network. Among them, it led to the discovery of the two-node feedback motif (2FB) in charge of the up-regulation of miRNA-target gene-TF and TF-mediated cascade motif and co-pointing motif (COP) responsible for the down-regulation of miRNA-target gene–TF. In this study, we found a correlation between miRNAs, TFs, and target genes using a gene regulatory network. We revealed the candidate 3-node motifs associated with the progression of DN. Therefore, detected molecular mechanisms, as well as the relationship between previous studies, demonstrated targets that can help in the discovery of a novel treatment for DN.

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鉴定参与肾小球糖尿病肾病的 miRNA-靶基因-转录因子调控网络功能基因

摘要基于数据库信息检索的基因调控方法可在 miRNA、转录因子（TFs）和基因水平上详细描述疾病进展的分子机制。此外，基因调控网络还能发现糖尿病肾病（DN）所涉及的 miRNA、TFs 和基因之间的相互作用，但其潜在机制仍不清楚。我们首先从 GEO 和 CTD 数据库中收集了与肾小球糖尿病肾病相关的基因。此外，我们还从公共数据库和 GEO 中收集了靶向基因的 miRNAs。此外，我们还从相关的公共数据库中收集了调控因子 TFs。之后，我们使用 FANMOD 软件探索了 TF-miRNA、miRNA-基因、TF-基因和 miRNA-TF 之间的调控关系。最后，在 Cytoscape 的帮助下，我们构建了一个由 miRNA、基因和 TF 组成的基因调控网络。FANMOD 软件中的全局 const 参数用于发现 miRNA、基因、TF 之间的相互作用，并在生成的网络中检测到 3 节点调控图案类型。其中，发现了负责 miRNA 靶基因-TF 上调的双节点反馈基团（2FB）和负责 miRNA 靶基因-TF 下调的 TF 介导级联基团和共点基团（COP）。本研究利用基因调控网络发现了 miRNA、TF 和靶基因之间的相关性。我们揭示了与 DN 进展相关的候选 3 节点模式。因此，检测到的分子机制以及以往研究之间的关系，展示了有助于发现 DN 新型疗法的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Russian Journal of Genetics 生物-遗传学

CiteScore

1.00

自引率

33.30%

发文量

126

审稿时长

1 months

期刊介绍： Russian Journal of Genetics is a journal intended to make significant contribution to the development of genetics. The journal publishes reviews and experimental papers in the areas of theoretical and applied genetics. It presents fundamental research on genetic processes at molecular, cell, organism, and population levels, including problems of the conservation and rational management of genetic resources and the functional genomics, evolutionary genomics and medical genetics.