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

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 AND 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.

journal_name

Med Sci Monit

journal_title

Medical science monitor : international medical journal of experimental and clinical research

authors

Zhou H,Tan L,Lu T,Xu K,Li C,Liu Z,Peng H,Shi R,Zhang G

doi

10.12659/MSM.924576

subject

Has Abstract

pub_date

2020-06-14 00:00:00

pages

e924576

eissn

1234-1010

issn

1643-3750

pii

924576

journal_volume

pub_type

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