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Issue 12, 2011
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Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver

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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.

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

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Publication details

The article was received on 02 Feb 2011, accepted on 02 Sep 2011 and first published on 03 Oct 2011


Article type: Paper
DOI: 10.1039/C1MB05041A
Citation: Mol. BioSyst., 2011,7, 3234-3244
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    Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver

    K. Kaur, A. K. Pandey, S. Srivastava, A. K. Srivastava and M. Datta, Mol. BioSyst., 2011, 7, 3234
    DOI: 10.1039/C1MB05041A

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