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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-gene” core network map for the three groups. A: The“TF–lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus healthy controls. B: the “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients without thymoma versus healthy controls. C: The “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus MG patients without thymoma.
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Fig6: The “TF–lncRNA-gene” core network map for the three groups. A: The“TF–lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus healthy controls. B: the “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients without thymoma versus healthy controls. C: The “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus MG patients without thymoma.

Mentions: Based on the results of the lncRNA co-expression analysis, we added the target genes into the “TF-lncRNA” network to determine the “TF-lncRNA-target genes” three-element network relationship. The networks were large and complex; therefore, we selected the top 300 relationships among lncRNAs, TFs and target genes to produce the core network map (Additional file 6). Figure 6A shows the core TF-lncRNA-target gene relationship for MG patients with thymoma versus healthy controls, containing 8 lncRNAs with disrupted expression (lncRNAs oebiotech_24272, oebiotech_23755, oebiotech_18319, oebiotech_13727, oebiotech_08281, A_21_P0008564, A_21_P0006010 and A_21_P0001906), 27 target genes and 1 core TF CTCF in this core map. Figure 6B shows the core TF-lncRNA-target gene relationship in MG patients without thymoma versus healthy controls, containing 10 lncRNAs with disrupted expression (lncRNAsoebiotech_25571, oebiotech_25019, oebiotech_23755, oebiotech_20751, oebiotech_20171, oebiotech_16583, oebiotech_07061, oebiotech_02627, oebiotech_00144 and A_21_P0007083), 41 target genes and 1 core TF CTCF in this core map. Figure 6C shows the core TF-lncRNA-target gene relationship in MG patients with thymoma versus MG patients without thymoma, containing 8 lncRNA with disrupted expression (lncRNAs oebiotech_22642, oebiotech_18319, oebiotech_18319, oebiotech_09353, oebiotech_06898, oebiotech_00715, A_21_P0010245, and A_21_P0009360), 27 target genes and1 core TF CTCF in this core map. The relationship among these three elements could be visualized using these three maps. Similar to the results shown in Figure 6A, the only core TF CTCF association regulated the expression of 8 lncRNAs and 27 target genes. The 8 lncRNAs might also regulate the expression of the 27 target genes. As observed for “CTCF-lncRNA oebiotech_24272-SOST” in this map, target genes, such as SOST, were co-expression genes for lncRNA oebiotech_24272. The transcription factor CTCF may regulate the expression of lncRNA oebiotech_24272and target genes, such as SOST. Thus, these maps provided valuable information concerning transcription factors, lncRNAs and target genes.Figure 6


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-gene” core network map for the three groups. A: The“TF–lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus healthy controls. B: the “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients without thymoma versus healthy controls. C: The “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus MG patients without thymoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig6: The “TF–lncRNA-gene” core network map for the three groups. A: The“TF–lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus healthy controls. B: the “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients without thymoma versus healthy controls. C: The “TF-lncRNA-gene” core network of the disturbed lncRNA expression in MG patients with thymoma versus MG patients without thymoma.
Mentions: Based on the results of the lncRNA co-expression analysis, we added the target genes into the “TF-lncRNA” network to determine the “TF-lncRNA-target genes” three-element network relationship. The networks were large and complex; therefore, we selected the top 300 relationships among lncRNAs, TFs and target genes to produce the core network map (Additional file 6). Figure 6A shows the core TF-lncRNA-target gene relationship for MG patients with thymoma versus healthy controls, containing 8 lncRNAs with disrupted expression (lncRNAs oebiotech_24272, oebiotech_23755, oebiotech_18319, oebiotech_13727, oebiotech_08281, A_21_P0008564, A_21_P0006010 and A_21_P0001906), 27 target genes and 1 core TF CTCF in this core map. Figure 6B shows the core TF-lncRNA-target gene relationship in MG patients without thymoma versus healthy controls, containing 10 lncRNAs with disrupted expression (lncRNAsoebiotech_25571, oebiotech_25019, oebiotech_23755, oebiotech_20751, oebiotech_20171, oebiotech_16583, oebiotech_07061, oebiotech_02627, oebiotech_00144 and A_21_P0007083), 41 target genes and 1 core TF CTCF in this core map. Figure 6C shows the core TF-lncRNA-target gene relationship in MG patients with thymoma versus MG patients without thymoma, containing 8 lncRNA with disrupted expression (lncRNAs oebiotech_22642, oebiotech_18319, oebiotech_18319, oebiotech_09353, oebiotech_06898, oebiotech_00715, A_21_P0010245, and A_21_P0009360), 27 target genes and1 core TF CTCF in this core map. The relationship among these three elements could be visualized using these three maps. Similar to the results shown in Figure 6A, the only core TF CTCF association regulated the expression of 8 lncRNAs and 27 target genes. The 8 lncRNAs might also regulate the expression of the 27 target genes. As observed for “CTCF-lncRNA oebiotech_24272-SOST” in this map, target genes, such as SOST, were co-expression genes for lncRNA oebiotech_24272. The transcription factor CTCF may regulate the expression of lncRNA oebiotech_24272and target genes, such as SOST. Thus, these maps provided valuable information concerning transcription factors, lncRNAs and target genes.Figure 6

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