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Systems biology of myasthenia gravis, integration of aberrant lncRNA and mRNA expression changes.

Luo Z, Li Y, Liu X, Luo M, Xu L, Luo Y, Xiao B, Yang H - BMC Med Genomics (2015)

Bottom Line: The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression.The results of the present study provide a perspective on lncRNA expression in MG.The results of the 'cis' and 'trans' analyses provide information concerning the modular regulation of lncRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. luozhaohui_xy@126.com.

ABSTRACT

Background: A novel class of transcripts, long non-coding RNAs (lncRNAs), has recently emerged as a key player in several biological processes, and important roles for these molecules have been reported in a number of complex human diseases, such as autoimmune diseases, neurological disorders, and various cancers. However, the aberrant lncRNAs implicated in myasthenia gravis (MG) remain unknown. The aim of the present study was to explore the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) and examine mRNA regulatory relationship networks among MG patients with or without thymoma.

Methods: Microarray assays were performed, and the outstanding differences between lncRNAs or mRNA expression were verified through RT-PCR. The lncRNAs functions were annotated for the target genes using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The potential regulatory relationships between the lncRNAs and target genes were analyzed using the 'cis' and 'trans' model. Outstanding lncRNAs were organized to generate a TF-lncRNA-gene network using Cytoscape software.

Results: The lncRNA and mRNA expression profile analysis revealed subsets of differentially expressed genes in MG patients with or without thymoma. A total of 12 outstanding dysregulated expression lncRNAs, such as lncRNA oebiotech_11933, were verified through real-time PCR. Several GO terms including the cellular response to interferon-γ, platelet degranulation, chemokine receptor binding and cytokine interactions were very important in MG pathogenesis. The chromosome locations of some lncRNAs and associated co-expression genes were demonstrated using 'cis' analysis. The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression. The outstanding lncRNAs in each group were implicated in the regulation of the TF-lncRNA-target gene network.

Conclusion: The results of the present study provide a perspective on lncRNA expression in MG. We identify a subset of aberrant lncRNAs and mRNAs as potential biomarkers for the diagnosis of MG. The GO and KEGG pathway analysis provides an annotation to determine the functions of these lncRNAs. The results of the 'cis' and 'trans' analyses provide information concerning the modular regulation of lncRNAs.

No MeSH data available.


Related in: MedlinePlus

The “TF-lncRNA” two-element networks for the three groups. A: The “TF-lncRNA” network between the MG with thymoma and healthy groups. B: The “TF-lncRNA” network between the MG without thymoma and healthy groups. C: The “TF-lncRNA” network between the MG with thymoma and MG without thymoma groups.
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Fig5: The “TF-lncRNA” two-element networks for the three groups. A: The “TF-lncRNA” network between the MG with thymoma and healthy groups. B: The “TF-lncRNA” network between the MG without thymoma and healthy groups. C: The “TF-lncRNA” network between the MG with thymoma and MG without thymoma groups.

Mentions: Currently, the known ‘trans’ regulation mechanism involves the factors mediating chromatin regulation and transcription. Using previously described methods [32,33], we calculated the lncRNA co-expression genes of chromatin regulators and transcription factors(TF) in the Encyclopedia of DNA Elements(ENCODE) [34] to identify common genes involved in lncRNA regulation. The “TF-lncRNA” two-element network was generated using Cytoscape software. The “TF-lncRNA” network is large and complex because numerous aberrant lncRNAs are involved. Therefore, we selected the top 100 largest relationships with the “TF-lncRNA” network to generate a core network map (Additional file 5). Figure 5A shows the “TF-lncRNA” core network map for MG patients with thymoma versus healthy controls. The transcription factor CTCF modulated the expression of 72 lncRNAs, whereas the TF TAF1 modulated the expression of 24 lncRNAs, and the TF MYC modulated the expression of 4 lncRNAs. Figure 5B shows the “TF” core network map for MG patients without thymoma versus healthy controls. The transcription factor CTCF modulated the expression of 60 lncRNAs, whereas the TF MYC modulated the expression of 9 lncRNAs. The “TF-lncRNA” core network map for MG patients without thymoma versus MG patients with thymoma indicated that TF TAF1 modulated the expression of 8 lncRNAs (Figure 5C). The transcription factor CTCF modulated the expression of 63 lncRNAs, the TF TAF1 modulated the expression of 26 lncRNAs, and the TF MYC modulated the expression of 11 lncRNAs. These three maps provide a vivid picture of the relationship between the lncRNAs and transcription factors and generate additional information for future studies.Figure 5


Systems biology of myasthenia gravis, integration of aberrant lncRNA and mRNA expression changes.

Luo Z, Li Y, Liu X, Luo M, Xu L, Luo Y, Xiao B, Yang H - BMC Med Genomics (2015)

The “TF-lncRNA” two-element networks for the three groups. A: The “TF-lncRNA” network between the MG with thymoma and healthy groups. B: The “TF-lncRNA” network between the MG without thymoma and healthy groups. C: The “TF-lncRNA” network between the MG with thymoma and MG without thymoma groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4380247&req=5

Fig5: The “TF-lncRNA” two-element networks for the three groups. A: The “TF-lncRNA” network between the MG with thymoma and healthy groups. B: The “TF-lncRNA” network between the MG without thymoma and healthy groups. C: The “TF-lncRNA” network between the MG with thymoma and MG without thymoma groups.
Mentions: Currently, the known ‘trans’ regulation mechanism involves the factors mediating chromatin regulation and transcription. Using previously described methods [32,33], we calculated the lncRNA co-expression genes of chromatin regulators and transcription factors(TF) in the Encyclopedia of DNA Elements(ENCODE) [34] to identify common genes involved in lncRNA regulation. The “TF-lncRNA” two-element network was generated using Cytoscape software. The “TF-lncRNA” network is large and complex because numerous aberrant lncRNAs are involved. Therefore, we selected the top 100 largest relationships with the “TF-lncRNA” network to generate a core network map (Additional file 5). Figure 5A shows the “TF-lncRNA” core network map for MG patients with thymoma versus healthy controls. The transcription factor CTCF modulated the expression of 72 lncRNAs, whereas the TF TAF1 modulated the expression of 24 lncRNAs, and the TF MYC modulated the expression of 4 lncRNAs. Figure 5B shows the “TF” core network map for MG patients without thymoma versus healthy controls. The transcription factor CTCF modulated the expression of 60 lncRNAs, whereas the TF MYC modulated the expression of 9 lncRNAs. The “TF-lncRNA” core network map for MG patients without thymoma versus MG patients with thymoma indicated that TF TAF1 modulated the expression of 8 lncRNAs (Figure 5C). The transcription factor CTCF modulated the expression of 63 lncRNAs, the TF TAF1 modulated the expression of 26 lncRNAs, and the TF MYC modulated the expression of 11 lncRNAs. These three maps provide a vivid picture of the relationship between the lncRNAs and transcription factors and generate additional information for future studies.Figure 5

Bottom Line: The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression.The results of the present study provide a perspective on lncRNA expression in MG.The results of the 'cis' and 'trans' analyses provide information concerning the modular regulation of lncRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China. luozhaohui_xy@126.com.

ABSTRACT

Background: A novel class of transcripts, long non-coding RNAs (lncRNAs), has recently emerged as a key player in several biological processes, and important roles for these molecules have been reported in a number of complex human diseases, such as autoimmune diseases, neurological disorders, and various cancers. However, the aberrant lncRNAs implicated in myasthenia gravis (MG) remain unknown. The aim of the present study was to explore the abnormal expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) and examine mRNA regulatory relationship networks among MG patients with or without thymoma.

Methods: Microarray assays were performed, and the outstanding differences between lncRNAs or mRNA expression were verified through RT-PCR. The lncRNAs functions were annotated for the target genes using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The potential regulatory relationships between the lncRNAs and target genes were analyzed using the 'cis' and 'trans' model. Outstanding lncRNAs were organized to generate a TF-lncRNA-gene network using Cytoscape software.

Results: The lncRNA and mRNA expression profile analysis revealed subsets of differentially expressed genes in MG patients with or without thymoma. A total of 12 outstanding dysregulated expression lncRNAs, such as lncRNA oebiotech_11933, were verified through real-time PCR. Several GO terms including the cellular response to interferon-γ, platelet degranulation, chemokine receptor binding and cytokine interactions were very important in MG pathogenesis. The chromosome locations of some lncRNAs and associated co-expression genes were demonstrated using 'cis' analysis. The results of the 'trans' analysis revealed that some TFs (i.e., CTCF, TAF1and MYC) regulate lncRNA and gene expression. The outstanding lncRNAs in each group were implicated in the regulation of the TF-lncRNA-target gene network.

Conclusion: The results of the present study provide a perspective on lncRNA expression in MG. We identify a subset of aberrant lncRNAs and mRNAs as potential biomarkers for the diagnosis of MG. The GO and KEGG pathway analysis provides an annotation to determine the functions of these lncRNAs. The results of the 'cis' and 'trans' analyses provide information concerning the modular regulation of lncRNAs.

No MeSH data available.


Related in: MedlinePlus