NDLI: Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver

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Molecular BioSystems Vol - 7 Issue - 9

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Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver

Content Provider	Royal Society of Chemistry (RSC)
Author	Datta, Malabika Srivastava, Swayamprakash Pandey, Amit K. Kaur, Kirandeep Srivastava, Arvind K.
Copyright Year	2011
Abstract	Aberrant microRNA expression patterns underlie the pathogenesis of diverse diseases, however in a disease as complex as diabetes where the liver exhibits deregulations of normal metabolic processes, the status and role of microRNAs are not yet completely understood. In a step towards unraveling this correlation, we assessed the global microRNA expression profiles in the control and diabetic (db/db) mice liver. These db/db mice were on a C57BLKS/J background and they exhibit diabetic phenotypes that are remarkably similar to those in humans. microRNA microarray profiling revealed 11 miRNAs to be up-regulated and 2 to be down-regulated in the db/db mice liver. Predicted targets of these differentially expressed microRNAs were retrieved from miRanda and TargetScan and the maximum number of commonly predicted targets mapped onto the Wnt signaling pathway that is otherwise conventionally associated with organogenesis and development. Towards validation of this prediction, we found that major components of the Wnt signaling pathway are inhibited in the db/db mice liver. A significant number of these down-regulated genes of the Wnt signaling pathway are predicted targets to the up-regulated miRNAs and specifically our results show that miR-34a and miR-22 decreased the protein levels of their targets. Overexpression of miR-34a and miR-22 and also inhibition of Wnt signaling using specific inhibitors led to increased lipid accumulation in HepG2 cells. Our data suggest that the Wnt signaling pathway could contribute towards the deregulated hepatic behavior in these animals and an altered hepatic miRNA signature could be playing a regulatory role herein.
Starting Page	3234
Ending Page	3244
Page Count	11
File Format	HTM / HTML PDF
ISSN	1742206X
Volume Number	7
Issue Number	12
Journal	Molecular BioSystems
DOI	10.1039/c1mb05041a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	MicroRNA Wnt signaling pathway Liver Regulation of gene expression Lipid metabolism Microarray TargetScan Diabetes mellitus type 2 Organogenesis
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biotechnology

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