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一种综合生物信息学方法鉴定局灶节段性肾小球硬化患者肾小管间质中的关键生物标志物，并构建 mRNA-miRNA-lncRNA/circRNA 网络。

An integrated bioinformatics approach to identify key biomarkers in the tubulointerstitium of patients with focal segmental glomerulosclerosis and construction of mRNA-miRNA-lncRNA/circRNA networks.

机构信息

College of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, China.

Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, China.

出版信息

Ren Fail. 2023;45(2):2284212. doi: 10.1080/0886022X.2023.2284212. Epub 2023 Nov 27.

DOI:10.1080/0886022X.2023.2284212
PMID:38013448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11001368/
Abstract

OBJECTIVE

The purpose of this study was to identify potential biomarkers in the tubulointerstitium of focal segmental glomerulosclerosis (FSGS) and comprehensively analyze its mRNA-miRNA-lncRNA/circRNA network.

METHODS

The expression data (GSE108112 and GSE200818) were downloaded from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/). Identification and enrichment analysis of differentially expressed genes (DEGs) were performed. the PPI networks of the DEGs were constructed and classified using the Cytoscape molecular complex detection (MCODE) plugin. Weighted gene coexpression network analysis (WGCNA) was used to identify critical gene modules. Least absolute shrinkage and selection operator regression analysis were used to screen for key biomarkers of the tubulointerstitium in FSGS, and the receiver operating characteristic curve was used to determine their diagnostic accuracy. The screening results were verified by quantitative real-time-PCR (qRT-PCR) and Western blot. The transcription factors (TFs) affecting the hub genes were identified by Cytoscape iRegulon. The mRNA-miRNA-lncRNA/circRNA network for identifying potential biomarkers was based on the starBase database.

RESULTS

A total of 535 DEGs were identified. MCODE obtained eight modules. The green module of WGCNA had the greatest association with the tubulointerstitium in FSGS. PPARG coactivator 1 alpha () was screened as a potential tubulointerstitial biomarker for FSGS and verified by qRT-PCR and Western blot. The TFs FOXO4 and FOXO1 had a regulatory effect on . The ceRNA network yielded 17 miRNAs, 32 lncRNAs, and 50 circRNAs.

CONCLUSIONS

may be a potential biomarker in the tubulointerstitium of FSGS. The ceRNA network contributes to the comprehensive elucidation of the mechanisms of tubulointerstitial lesions in FSGS.

摘要

目的

本研究旨在鉴定局灶节段性肾小球硬化（FSGS）小管间质中的潜在生物标志物，并全面分析其 mRNA-miRNA-lncRNA/circRNA 网络。

方法

从基因表达综合数据库（https://www.ncbi.nlm.nih.gov/geo/）下载表达数据（GSE108112 和 GSE200818）。对差异表达基因（DEGs）进行鉴定和富集分析。使用 Cytoscape 分子复合物检测（MCODE）插件构建和分类 DEGs 的 PPI 网络。采用加权基因共表达网络分析（WGCNA）鉴定关键基因模块。使用最小绝对收缩和选择算子回归分析筛选 FSGS 小管间质的关键生物标志物，并使用受试者工作特征曲线确定其诊断准确性。通过定量实时-PCR（qRT-PCR）和 Western blot 验证筛选结果。使用 Cytoscape iRegulon 鉴定影响枢纽基因的转录因子（TFs）。基于 starBase 数据库构建 mRNA-miRNA-lncRNA/circRNA 网络以鉴定潜在生物标志物。

结果

共鉴定出 535 个 DEGs。MCODE 获得了 8 个模块。WGCNA 的绿色模块与 FSGS 的小管间质相关性最大。筛选出过氧化物酶体增殖物激活受体共激活因子 1 阿尔法（）作为 FSGS 的潜在小管间质生物标志物，并通过 qRT-PCR 和 Western blot 进行验证。TFs FOXO4 和 FOXO1 对具有调节作用。ceRNA 网络产生了 17 个 miRNA、32 个 lncRNA 和 50 个 circRNA。

结论

可能是 FSGS 小管间质中的潜在生物标志物。ceRNA 网络有助于全面阐明 FSGS 小管间质损伤的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/394b5657639e/IRNF_A_2284212_F0013_C.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/385a29ee28c6/IRNF_A_2284212_F0008_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/a4751c7afb8f/IRNF_A_2284212_F0009_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/f9eb6b8ce9ba/IRNF_A_2284212_F0010_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/e208709f1f3f/IRNF_A_2284212_F0011a_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/49330ef96fb1/IRNF_A_2284212_F0011b_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5263/11001368/d16efe203e7b/IRNF_A_2284212_F0011c_C.jpg
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