Dissecting genetics of cutaneous miRNA in a mouse model of an autoimmune blistering disease

MicroRNAs (miRNAs) are small endogenous non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and such altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA...

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Bibliographic Details
Published in:BMC genomics 2016-02, Vol.17 (114), p.112-112, Article 112
Main Authors: Gupta, Yask, Möller, Steffen, Witte, Mareike, Belheouane, Meriem, Sezin, Tanya, Hirose, Misa, Vorobyev, Artem, Niesar, Felix, Bischof, Julia, Ludwig, Ralf J, Zillikens, Detlef, Sadik, Christian D, Restle, Tobias, Häsler, Robert, Baines, John F, Ibrahim, Saleh M
Format: Article
Language:English
Subjects:
Animals
Autoimmune diseases
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Blister - genetics
Blister - immunology
Disease Models, Animal
Epistasis, Genetic
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Genetic Association Studies
Genetic Predisposition to Disease
Genetic regulation
Genomics
Identification and classification
Mice
MicroRNA
MicroRNAs - genetics
Observations
Polymorphism, Single Nucleotide
Properties
Quantitative Trait Loci
Skin - metabolism
Skin - pathology
Skin diseases
Transcriptome
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Summary:MicroRNAs (miRNAs) are small endogenous non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and such altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA expression is genetically controlled similar to the transcription of protein-coding genes and previous studies identified quantitative trait loci (QTL) for miRNA expression in the liver. So far, little attention has been paid to miRNA expression in the skin. Moreover, epistatic control of miRNA expression remains unknown. In this study, we characterize genetic regulation of cutaneous miRNA and their correlation with skin inflammation using a previously established murine autoimmune-prone advanced intercross line. We identified in silico 42 eQTL controlling the expression of 38 cutaneous miRNAs and furthermore found two chromosomal hot-spots on chromosomes 2 and 8 that control the expression of multiple miRNAs. Moreover, for 8 miRNAs an interacting effect from pairs of SNPs was observed. Combining the constraints on genes from the statistical interaction of their loci and further using curated protein interaction networks, the number of candidate genes for association of miRNAs was reduced to a set of several genes. A cluster analysis identified miR-379 and miR-223 to be associated with EBA severity/onset, where miR-379 was observed to be associated to loci on chromosome 6. The murine advanced intercross line allowed us to identify the genetic loci regulating multiple miRNA in skin. The recurrence of trans-eQTL and epistasis suggest that cutaneous miRNAs are regulated by yet an unexplored complex gene networks. Further, using co-expression analysis of miRNA expression levels we showed that multiple miRNA contribute to multiple pathways that might be involved in pathogenesis of autoimmune skin blistering disease. Specifically, we provide evidence that miRNA such as miR-223 and miR-379 may play critical role in disease progression and severity.
ISSN:1471-2164
1471-2164
DOI:10.1186/s12864-016-2455-2