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Int. J. Mol. Sci. 2016, 17(4), 475; doi:10.3390/ijms17040475

Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes

1
Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany
2
Chair for Clinical Bioinformatics, Building E2.1, 66123 Saarbruecken, Germany
3
Center for Bioinformatics, Saarland University, Building E.1.1, 66041 Saarbruecken, Germany
4
Developmental Biochemistry, Biocenter, and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, 97074 Wuerzburg, Germany
5
Department of Pediatric Oncology and Hematology, Medical School, Saarland University, 66421 Homburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Y-h. Taguchi
Received: 28 January 2016 / Revised: 18 March 2016 / Accepted: 22 March 2016 / Published: 30 March 2016
(This article belongs to the Special Issue MicroRNA Regulation)
View Full-Text   |   Download PDF [1836 KB, uploaded 30 March 2016]   |  

Abstract

Wilms tumor (WT) is the most common childhood renal cancer. Recent findings of mutations in microRNA (miRNA) processing proteins suggest a pivotal role of miRNAs in WT genesis. We performed miRNA expression profiling of 36 WTs of different subtypes and four normal kidney tissues using microarrays. Additionally, we determined the gene expression profile of 28 of these tumors to identify potentially correlated target genes and affected pathways. We identified 85 miRNAs and 2107 messenger RNAs (mRNA) differentially expressed in blastemal WT, and 266 miRNAs and 1267 mRNAs differentially expressed in regressive subtype. The hierarchical clustering of the samples, using either the miRNA or mRNA profile, showed the clear separation of WT from normal kidney samples, but the miRNA pattern yielded better separation of WT subtypes. A correlation analysis of the deregulated miRNA and mRNAs identified 13,026 miRNA/mRNA pairs with inversely correlated expression, of which 2844 are potential interactions of miRNA and their predicted mRNA targets. We found significant upregulation of miRNAs-183, -301a/b and -335 for the blastemal subtype, and miRNAs-181b, -223 and -630 for the regressive subtype. We found marked deregulation of miRNAs regulating epithelial to mesenchymal transition, especially in the blastemal subtype, and miRNAs influencing chemosensitivity, especially in regressive subtypes. Further research is needed to assess the influence of preoperative chemotherapy and tumor infiltrating lymphocytes on the miRNA and mRNA patterns in WT. View Full-Text
Keywords: miRNA; Wilms tumor; blastemal; regressive miRNA; Wilms tumor; blastemal; regressive
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Ludwig, N.; Werner, T.V.; Backes, C.; Trampert, P.; Gessler, M.; Keller, A.; Lenhof, H.-P.; Graf, N.; Meese, E. Combining miRNA and mRNA Expression Profiles in Wilms Tumor Subtypes. Int. J. Mol. Sci. 2016, 17, 475.

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