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miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation
The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatin-induced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA express...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625446/ https://www.ncbi.nlm.nih.gov/pubmed/31257474 http://dx.doi.org/10.3892/mmr.2019.10383 |
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author | Zhang, Chunmei Ma, Piyong Zhao, Zhongyan Jiang, Nan Lian, Dede Huo, Pengfei Yang, Hailing |
author_facet | Zhang, Chunmei Ma, Piyong Zhao, Zhongyan Jiang, Nan Lian, Dede Huo, Pengfei Yang, Hailing |
author_sort | Zhang, Chunmei |
collection | PubMed |
description | The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatin-induced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA expression (GSE66761) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the linear models for microarray data method and mRNA targets of DEMs were predicted using the miRWalk2.0 database. The crucial DEGs were screened by constructing a protein-protein interaction (PPI) network and module analysis. Functions of target genes were analyzed using the database for annotation, visualization and integrated discovery. Small molecule drugs were predicted using the connectivity map database. As a result, 5 DEMs were identified to be shared and oppositely expressed in comparisons between AKI model and control groups, and between MSC treatment and AKI model groups. The 103 DEGs were overlapped with the target genes of 5 common DEMs, and the resulting list was used for constructing the miRNA-mRNA regulatory network, including rno-miR-210/Serpine1 and rno-miR-378/Fos. Serpine1 (degree=17) and Fos (degree=42) were predicted to be hub genes according to the topological characteristic of degree in the PPI network. Function analysis indicated Serpine1 and Fos may be inflammation-related. Furthermore, gliclazide was suggested to be a potential drug for the treatment of AKI because the enrichment score was the closest to −1 (−0.9). In conclusion, it can be speculated that gliclazide may have a similar mechanism to MSC as a potential therapeutic agent for cisplatin-induced AKI, by regulating miR-210/Serpine1 and miR-378-/Fos-mediated inflammation and cell apoptosis. |
format | Online Article Text |
id | pubmed-6625446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-66254462019-07-31 miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation Zhang, Chunmei Ma, Piyong Zhao, Zhongyan Jiang, Nan Lian, Dede Huo, Pengfei Yang, Hailing Mol Med Rep Articles The present study aimed to identify microRNAs (miRNAs) that may be crucial for the mechanism of mesenchymal stem cell (MSC) treatment in cisplatin-induced acute kidney injury (AKI) and to investigate other potential drugs that may have a similar function. Transcriptomics (GSE85957) and miRNA expression (GSE66761) datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the linear models for microarray data method and mRNA targets of DEMs were predicted using the miRWalk2.0 database. The crucial DEGs were screened by constructing a protein-protein interaction (PPI) network and module analysis. Functions of target genes were analyzed using the database for annotation, visualization and integrated discovery. Small molecule drugs were predicted using the connectivity map database. As a result, 5 DEMs were identified to be shared and oppositely expressed in comparisons between AKI model and control groups, and between MSC treatment and AKI model groups. The 103 DEGs were overlapped with the target genes of 5 common DEMs, and the resulting list was used for constructing the miRNA-mRNA regulatory network, including rno-miR-210/Serpine1 and rno-miR-378/Fos. Serpine1 (degree=17) and Fos (degree=42) were predicted to be hub genes according to the topological characteristic of degree in the PPI network. Function analysis indicated Serpine1 and Fos may be inflammation-related. Furthermore, gliclazide was suggested to be a potential drug for the treatment of AKI because the enrichment score was the closest to −1 (−0.9). In conclusion, it can be speculated that gliclazide may have a similar mechanism to MSC as a potential therapeutic agent for cisplatin-induced AKI, by regulating miR-210/Serpine1 and miR-378-/Fos-mediated inflammation and cell apoptosis. D.A. Spandidos 2019-08 2019-06-13 /pmc/articles/PMC6625446/ /pubmed/31257474 http://dx.doi.org/10.3892/mmr.2019.10383 Text en Copyright: © Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhang, Chunmei Ma, Piyong Zhao, Zhongyan Jiang, Nan Lian, Dede Huo, Pengfei Yang, Hailing miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title | miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title_full | miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title_fullStr | miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title_full_unstemmed | miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title_short | miRNA-mRNA regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for miR-210/Serpine1 and miR-378/Fos in regulating inflammation |
title_sort | mirna-mrna regulatory network analysis of mesenchymal stem cell treatment in cisplatin-induced acute kidney injury identifies roles for mir-210/serpine1 and mir-378/fos in regulating inflammation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625446/ https://www.ncbi.nlm.nih.gov/pubmed/31257474 http://dx.doi.org/10.3892/mmr.2019.10383 |
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