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Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis

View Article: PubMed Central - PubMed

ABSTRACT

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.

No MeSH data available.


Pathway analysis of the differentially expressed mRNAs.(A) The 30 most significant pathways of up-regulated mRNAs. (B) The significant pathways of the down-regulated mRNAs. Enrichment score values were calculated as -ln (p values). (C) Distinct and shared pathways in DM subgroups “ILD+ Jo1−”, “ILD− Jo1−”, “ILD+ Jo1+”. The detailed information of the pathways involved in the figure is presented in Supplementary datasheet 4.
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f5: Pathway analysis of the differentially expressed mRNAs.(A) The 30 most significant pathways of up-regulated mRNAs. (B) The significant pathways of the down-regulated mRNAs. Enrichment score values were calculated as -ln (p values). (C) Distinct and shared pathways in DM subgroups “ILD+ Jo1−”, “ILD− Jo1−”, “ILD+ Jo1+”. The detailed information of the pathways involved in the figure is presented in Supplementary datasheet 4.

Mentions: We further performed pathway analysis on the differentially expressed mRNAs according to the following databases: the latest version of Kyoto Encyclopedia of Genes and Genomes (KEGG) database (http://www.genome.jp/kegg), PID (http://pid.nci.nih.gov/), BioCyc (http://biocys.org/), Reactome (http://www.reactome.org/), and Panther (http://www.pantherdb.org/). Consequently, the biological pathways that were significantly enriched with these differentially expressed mRNAs were uncovered. The results showed that a total of 74 pathways were associated with the up-regulated mRNA transcripts, with “Interferon Signaling” recognized as the most enriched network. Furthermore, we also found 6 pathways that were significantly related to down-regulated mRNAs, “Erythrocytes take up oxygen and release carbon dioxide” being the most enriched one. The top 30 enriched pathways of up-regulated mRNAs and down-regulated mRNAs are shown in Fig. 5A,B.


Transcriptomic profiling of long non-coding RNAs in dermatomyositis by microarray analysis
Pathway analysis of the differentially expressed mRNAs.(A) The 30 most significant pathways of up-regulated mRNAs. (B) The significant pathways of the down-regulated mRNAs. Enrichment score values were calculated as -ln (p values). (C) Distinct and shared pathways in DM subgroups “ILD+ Jo1−”, “ILD− Jo1−”, “ILD+ Jo1+”. The detailed information of the pathways involved in the figure is presented in Supplementary datasheet 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015085&req=5

f5: Pathway analysis of the differentially expressed mRNAs.(A) The 30 most significant pathways of up-regulated mRNAs. (B) The significant pathways of the down-regulated mRNAs. Enrichment score values were calculated as -ln (p values). (C) Distinct and shared pathways in DM subgroups “ILD+ Jo1−”, “ILD− Jo1−”, “ILD+ Jo1+”. The detailed information of the pathways involved in the figure is presented in Supplementary datasheet 4.
Mentions: We further performed pathway analysis on the differentially expressed mRNAs according to the following databases: the latest version of Kyoto Encyclopedia of Genes and Genomes (KEGG) database (http://www.genome.jp/kegg), PID (http://pid.nci.nih.gov/), BioCyc (http://biocys.org/), Reactome (http://www.reactome.org/), and Panther (http://www.pantherdb.org/). Consequently, the biological pathways that were significantly enriched with these differentially expressed mRNAs were uncovered. The results showed that a total of 74 pathways were associated with the up-regulated mRNA transcripts, with “Interferon Signaling” recognized as the most enriched network. Furthermore, we also found 6 pathways that were significantly related to down-regulated mRNAs, “Erythrocytes take up oxygen and release carbon dioxide” being the most enriched one. The top 30 enriched pathways of up-regulated mRNAs and down-regulated mRNAs are shown in Fig. 5A,B.

View Article: PubMed Central - PubMed

ABSTRACT

Long non-coding RNAs (lncRNAs) are prevalently transcribed in the genome and have been found to be of functional importance. However, the potential roles of lncRNAs in dermatomyositis (DM) remain unknown. In this study, a lncRNA + mRNA microarray analysis was performed to profile lncRNAs and mRNAs from 15 treatment-naive DM patients and 5 healthy controls. We revealed a total of 1198 lncRNAs (322 up-regulated and 876 down-regulated) and 1213 mRNAs (665 up-regulated and 548 down-regulated) were significantly differentially expressed in DM patients compared with the healthy controls (fold change>2, P < 0.05). Subgrouping DM patients according to the presence of interstitial lung disease and anti-Jo-1 antibody revealed different expression patterns of the lncRNAs. Pathway and gene ontology analysis for the differentially expressed mRNAs confirmed that type 1 interferon signaling was the most significantly dysregulated pathway in all DM subgroups. In addition, distinct pathways that uniquely associated with DM subgroup were also identified. Bioinformatics prediction suggested that linc-DGCR6-1 may be a lncRNA that regulates type 1 interferon-inducible gene USP18, which was found highly expressed in the perifascicular areas of the muscle fibers of DM patients. Our findings provide an overview of aberrantly expressed lncRNAs in DM muscle and further broaden the understanding of DM pathogenesis.

No MeSH data available.