What is it about?
It is well known that small RNAs called microRNAs can regulate the expression and translation of messenger RNAs (mRNAs) into proteins. Using biochemical methods and deep sequencing of RNA, we profiled the global interactions of microRNAs and mRNAs in a cellular model of calcineurin inhibitor nephrotoxicity. This approach allowed us to uncover the cellular pathways in kidney cells regulated by microRNAs after drug treatment and provide new insights into the toxic side-effects of immunosuppressant medicines.
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Why is it important?
Calcineurin inhibitor nephrotoxicity (CIN) still remains a hindrance to successful long-term transplantation outcomes. Our findings represent a catalog of miRNA and mRNA expression and interactions in CIN. Differential expression analysis in this model elucidates the cellular pathways directly and indirectly modulated by the drug cyclosporine. Further, by identifying the network of miRNA:mRNA interactions in this model, we have underscored the importance of post-transcriptional regulation in understanding the mechanisms of toxicity in CIN. These interactions provide novel insight into calcineurn-independent mechanisms of cyclosporine action and present novel potential therapeutic targets.
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This page is a summary of: Defining a microRNA-mRNA interaction map for calcineurin inhibitor induced nephrotoxicity, American Journal of Transplantation, October 2017, Wiley, DOI: 10.1111/ajt.14503.
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