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Identification of Target Genes and Transcription Factors in Mice with LMNA -Related Dilated Cardiomyopathy by Integrated Bioinformatic Analyses

Authors
  • Zhou, Honghua1
  • Tan, Liao1
  • Lu, Ting2
  • Xu, Kai2
  • Li, Chan1
  • Liu, Zhaoya3
  • Peng, Huihui4
  • Shi, RuiZheng1
  • Zhang, Guogang2
  • 1 Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • 2 Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • 3 Department of Geriatrics, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
  • 4 Department of Cardiovascular Medicine, The Affiliated Puren Hospital of Wuhan University of Science and Technology, Wuhan University of Science and Technology, Wuhan, Hubei, P.R. China
Type
Published Article
Journal
Medical Science Monitor
Publisher
"International Scientific Information, Inc."
Publication Date
Jun 14, 2020
Volume
26
Identifiers
DOI: 10.12659/MSM.924576
PMID: 32581210
PMCID: PMC7313426
Source
PubMed Central
Keywords
License
Green

Abstract

Background Dilated cardiomyopathy (DCM), which is characterized by enlarged ventricular dimensions and systolic dysfunction, is the most common type of cardiomyopathy. Mutations in the LMNA gene are reported in approximately 10% of familial DCM cases. However, the mechanism of LMNA mutations in human DCM remains unclear. Material/Methods We used the GSE36502 and GSE123916 datasets to obtain gene expression profiles from LMNA -related DCM mice and to identify differentially expressed genes (DEGs). Crucial function and pathway enrichment analyses of DEGs were performed. Protein–protein interaction (PPI) network analysis was carried out to identify the top 10 hub genes, which were validated using reverse transcription-polymerase chain reaction (RT-PCR) to find target genes. Weighted gene co-expression network analysis (WGCNA) was used to explore the module relevant to external traits of LMNA -related DCM mice. Transcription factors (TFs) for the selected genes were analyzed using NetworkAnalyst. Results A total of 156 common DEGs (co-DEGs) were identified, including 80 up-regulated and 76 down-regulated genes. The enriched biological functions and pathways were oxidative stress, regulation of apoptosis, regulation of fibrosis, and MAPK pathways. Five target genes ( Timp1 , Hmox1 , Spp1 , Atf3 , and Adipoq ) were verified after RT-PCR. Most co-DEGs were discovered to be related to the development of external traits. Three TFs (ELF1, ETS1, and NRF1) showed close interactions with the hub genes. Conclusions Our study used integrated bioinformatic analyses and revealed some important genes in mice with LMNA -related DCM, which could provide novel insights into the mechanism underlying human LMNA -related DCM.

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