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. 2016 Aug 9;7(32):52270-52280.
doi: 10.18632/oncotarget.10586.

Bioinformatics facilitating the use of microarrays to delineate potential miRNA biomarkers in aristolochic acid nephropathy

Yana Lv  1 , Yumei Que  2 , Qiao Su  3   2 , Qiang Li  3   2 , Xi Chen  1 , Haitao Lu  3   4
Affiliations

Bioinformatics facilitating the use of microarrays to delineate potential miRNA biomarkers in aristolochic acid nephropathy

Yana Lv et al. Oncotarget. .

Abstract

Aristolochic acid nephropathy (AAN) is a rapidly progressive acute or chronic tubulointerstitial nephritis (TIN). The present study attempted to explore the molecular mechanisms underlying the miRNA-directed development of AAN. Our differentially expressed analysis identified 11 DE-miRNAs and retrieved the target genes of these DE-miRNAs; then, network analysis and functional analysis further identified 6 DE-miRNAs (has-miR-192, has-miR-194, has-miR-542-3p, has-miR-450a, has-miR-584, has-miR-33a) as phenotypic biomarkers of AAN. Surprisingly, of has-miR-192 has been reported to be associated with the pathogenesis of AAN, and has-miR-194, has-miR-542-3p and has-miR-450a was first-time identified to link to the development of AAN. In addition, the expressional changes of has-miR-584 and has-miR-33a may be associated with the development of AAN as well, which must be further confirmed by the associated experiments. Taken together, our work reveals for the first time the regulatory mechanisms of miRNAs in the development of AAN and this will contribute to miRNA-based diagnosis and treatment of AAN.

Keywords: aristolochic acid nephropathy; biomarkers; functional analysis; microRNAs; network biology.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Regulatory network of differentially expressed miRNA-genes
In the miRNA-gene regulation network, yellow squares denote miRNAs. Target genes are represented in bright green, light blue, orange and red circles based on the number of regulatory relationships between the miRNAs and target genes. Bright green indicates one regulatory relationship, light blue denotes two regulatory relationships, orange denotes three regulatory relationships, and red indicates four regulatory relationships.
Figure 2
Figure 2. Regulatory-network analysis of miRNA-pathways
In the miRNA-pathway regulation network, yellow squares represent miRNAs, and the coloured circles denote pathways in light blue, pink, green and red based on the number of regulatory relationships between significant pathways and miRNAs. Light blue represents one regulatory relationship, pink represents two regulatory relationships, green represents three regulatory relationships, and red represents four regulatory relationships.
Figure 3
Figure 3. Information for the degrees of the DE-miRNAs
In the two networks, the degrees represent the numbers of connections between miRNAs and target genes/pathways.
Figure 4
Figure 4. Distribution of the GO terms for the target genes of DE-miRNAs
A. The GO terms for the target genes of hsa-miR-192, hsa-miR-542-3P, and hsa-miR-450a were classified into biological process by WEGO. B. The GO terms for the target genes of hsa-miR-33a, hsa-miR-194, and hsa-miR-584 were classified into biological processes by WEGO.
See this image and copyright information in PMC

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