Open Access

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

  • Authors:
    • Chunmei Zhang
    • Piyong Ma
    • Zhongyan Zhao
    • Nan Jiang
    • Dede Lian
    • Pengfei Huo
    • Hailing Yang
  • View Affiliations

  • Published online on: June 13, 2019     https://doi.org/10.3892/mmr.2019.10383
  • Pages: 1509-1522
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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August-2019
Volume 20 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang C, Ma P, Zhao Z, Jiang N, Lian D, Huo P and Yang H: 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. Mol Med Rep 20: 1509-1522, 2019
APA
Zhang, C., Ma, P., Zhao, Z., Jiang, N., Lian, D., Huo, P., & Yang, H. (2019). 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. Molecular Medicine Reports, 20, 1509-1522. https://doi.org/10.3892/mmr.2019.10383
MLA
Zhang, C., Ma, P., Zhao, Z., Jiang, N., Lian, D., Huo, P., Yang, H."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". Molecular Medicine Reports 20.2 (2019): 1509-1522.
Chicago
Zhang, C., Ma, P., Zhao, Z., Jiang, N., Lian, D., Huo, P., Yang, H."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". Molecular Medicine Reports 20, no. 2 (2019): 1509-1522. https://doi.org/10.3892/mmr.2019.10383