scholarly journals Network Analysis Identifies Gene Regulatory Network Indicating the Role of RUNX1 in Human Intervertebral Disc Degeneration

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 771 ◽  
Author(s):  
Nazir M. Khan ◽  
Martha E Diaz-Hernandez ◽  
Steven M. Presciutti ◽  
Hicham Drissi
Keyword(s):  
Transcription Factors ◽  
Network Analysis ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Regulatory Network ◽  
Interaction Network ◽  
Functional Enrichment ◽  
Network Cluster ◽  
Chemokine Signaling

Intervertebral disc (IVD) degeneration (IDD) is a multifactorial physiological process which is often associated with lower back pain. Previous studies have identified some molecular markers associated with disc degeneration, which despite their significant contributions, have provided limited insight into the etiology of IDD. In this study, we utilized a network medicine approach to uncover potential molecular mediators of IDD. Our systematic analyses of IDD associated with 284 genes included functional annotation clustering, interaction networks, network cluster analysis and Transcription factors (TFs)-target gene network analysis. The functional enrichment and protein–protein interaction network analysis highlighted the role of inflammatory genes and cytokine/chemokine signaling in IDD. Moreover, sub-network analysis identified significant clusters possessing organized networks of 24 cytokine and chemokine genes, which may be considered as key modulators for IDD. The expression of these genes was validated in independent microarray datasets. In addition, the regulatory network analysis identified the role of multiple transcription factors, with RUNX1 being a master regulator in the pathogenesis of IDD. Our analyses highlighted the role of cytokine genes and interacting pathways in IDD and further improved our understanding of the genetic mechanisms underlying IDD.

scholarly journals Identification of Key Genes and Pathways Associated With Pathogenesis of Intervertebral Disc Degeneration by Integrated miRNA-mRNA Network Analysis

2021 ◽  
Author(s):  
Tao Lan ◽  
Ning-dao Li ◽  
Zhe Shen ◽  
Xiao-sheng Chen ◽  
Shi-yu Hu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Critical Pathways ◽  
Underlying Mechanisms

Abstract Background: Intervertebral disc degeneration (IDD) is one of the most common cause of low back pain. Previous studies have suggested that miRNAs are associated with the pathogenesis of IDD. However, the underlying mechanisms remain unclear based on inconsistent results of available literatures. In addition, integrated miRNA-mRNA comprehensive analysis is limited. Material/Methods: In this study, we investigated the profiles of differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) and constructed a miRNA-mRNA regulatory network. First, transcription factors and target genes of DEMIs were predicted. Then, an intersection between DEMIs predicted genes and DEGs were performed to screen out the most significant differential expressed common genes. Results: A total of 65 DEMIs and 61 common target genes were identified from datasets. Functional enrichment analysis showed that most genes were mainly involved in extracellular matrix organization and extracellular structure organization. Furthermore, DEGs were primarily enriched in PI3K−Akt signaling pathway, ECM−receptor interaction, focal adhesion and p53 signaling pathway, indicating that these pathways may be the critical pathways.Conclusions: In summary, several important miRNAs, as well as their related target genes and transcription factors in the pathogenesis of IDD were identified from our bioinformatic analysis, which may provide insights into underlying mechanisms and offer potential target genes for the treatment of IDD.

scholarly journals Role of the miR-133a-5p/FBXO6 axis in the regulation of intervertebral disc degeneration

2021 ◽  
Vol 29 ◽  
pp. 123-133
Author(s):  
Xian-Fa Du ◽  
Hai-Tao Cui ◽  
He-Hai Pan ◽  
Jun Long ◽  
Hao-Wen Cui ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration

scholarly journals Screening Driving Transcription Factors in the Processing of Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Integrated Analysis ◽  
Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

Role of autophagy in intervertebral disc degeneration

2021 ◽  
Author(s):  
Rebecca Kritschil ◽  
Melanie Scott ◽  
Gwendolyn Sowa ◽  
Nam Vo
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration

Genetic aspects of intervertebral disc degeneration

2015 ◽  
Vol 26 (5) ◽  
pp. 581-606 ◽  
Author(s):  
Sara Hanaei ◽  
Sina Abdollahzade ◽  
Alireza Khoshnevisan ◽  
Christopher K. Kepler ◽  
Nima Rezaei
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Genetic Factors ◽  
Wide Spectrum ◽  
Nucleotide Polymorphisms ◽  
Disc Disease ◽  
Multifactorial Diseases ◽  
Common Causes

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

scholarly journals Potential Role of lncRNAs in Contributing to Pathogenesis of Intervertebral Disc Degeneration Based on Microarray Data

2015 ◽  
Vol 21 ◽  
pp. 3449-3458 ◽  
Author(s):  
Yu Chen ◽  
Haijian Ni ◽  
Yingchuan Zhao ◽  
Kai Chen ◽  
Ming Li ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Microarray Data ◽  
Intervertebral Disc Degeneration ◽  
Potential Role
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