Bioinformatics and Experimental Analyses Reveal NFIC as an Upstream Transcriptional Regulator for Ischemic Cardiomyopathy.
Yang YeQiao JinQian GongAoqi LiMinghao SunSibo JiangYulan JinZhe ZhangJin HeLenan ZhuangPublished in: Genes (2022)
Ischemic cardiomyopathy (ICM) caused by coronary artery disease always leads to myocardial infarction and heart failure. Identification of novel transcriptional regulators in ICM is an effective method to establish new diagnostic and therapeutic strategies. In this study, we used two RNA-seq datasets and one microarray dataset from different studies, including 25 ICM and 21 non-failing control (NF) samples of human left ventricle tissues for further analysis. In total, 208 differentially expressed genes (DEGs) were found by combining two RNA-seq datasets with batch effects removed. GO and KEGG analyses of DEGs indicated that the response to wounding, positive regulation of smooth muscle contraction, chromatin, PI3K-Akt signaling pathway, and transporters pathways are involved in ICM. Simple Enrichment Analysis found that NFIC-binding motifs are enriched in promoter regions of downregulated genes. The Gene Importance Calculator further proved that NFIC is vital. NFIC and its downstream genes were verified in the validating microarray dataset. Meanwhile, in rat cardiomyocyte cell line H9C2 cells, two genes ( Tspan1 and Hopx ) were confirmed, which decreased significantly along with knocking down Nfic expression. In conclusion, NFIC participates in the ICM process by regulating TSPAN1 and HOPX . NFIC and its downstream genes may be marker genes and potential diagnostic and therapeutic targets for ICM.
Keyphrases
- rna seq
- genome wide
- bioinformatics analysis
- signaling pathway
- pi k akt
- single cell
- heart failure
- genome wide identification
- transcription factor
- smooth muscle
- gene expression
- dna methylation
- cell cycle arrest
- coronary artery disease
- induced apoptosis
- genome wide analysis
- copy number
- cell proliferation
- oxidative stress
- ischemia reperfusion injury
- endothelial cells
- coronary artery
- cardiovascular disease
- immune response
- poor prognosis
- risk assessment
- dna binding
- cardiovascular events
- nuclear factor
- anaerobic digestion
- heat shock protein