Abstract
IntroductionEmerging evidence suggests that microRNAs (miRNAs) are crucially involved in tumorigenesis and that paired expression profiles of miRNAs and mRNAs can be used to identify functional miRNA-target relationships with high precision. However, no studies have applied integrated analysis to miRNA and mRNA profiles in chordomas. The purpose of this study was to provide insights into the pathogenesis of chordomas by using this integrated analysis method.MethodsDifferentially expressed miRNAs and mRNAs of chordomas (n = 3) and notochord tissues (n = 3) were analyzed by using microarrays with hierarchical clustering analysis. Subsequently, the target genes of the differentially expressed miRNAs were predicted and overlapped with the differentially expressed mRNAs. Then, GO and pathway analyses were performed for the intersecting genes.ResultsThe microarray analysis indicated that 33 miRNAs and 2,791 mRNAs were significantly dysregulated between the two groups. Among the 2,791 mRNAs, 911 overlapped with putative miRNA target genes. A pathway analysis showed that the MAPK pathway was consistently enriched in the chordoma tissue and that miR-149-3p, miR-663a, miR-1908, miR-2861 and miR-3185 likely play important roles in the regulation of MAPK pathways. Furthermore, the Notch signaling pathway and the loss of the calcification or ossification capacity of the notochord may also be involved in chordoma pathogenesis.ConclusionThis study provides an integrated dataset of the miRNA and mRNA profiles in chordomas, and the results demonstrate that not only the MAPK pathway and its related miRNAs but also the Notch pathway may be involved in chordoma development. The occurrence of chordoma may be associated with dysfunctional calcification or ossification of the notochord.
Highlights
Emerging evidence suggests that microRNAs are crucially involved in tumorigenesis and that paired expression profiles of miRNAs and mRNAs can be used to identify functional miRNA-target relationships with high precision
Paraffin sections from the fixed chordoma tissues were cut at 5 mm and stained with hematoxylin and eosin (H&E) as well as antibodies against cytokeratin, S100 and brachyury proteins [11,12,13,14] (Figure 1)
4.1 Integrated miRNA-mRNA Analysis of Chordomas Cancer is a complex genetic disease that involves structural and regulatory abnormalities in both coding and non-coding genes, and abnormal expression of miRNA appears to be representative of aberrant gene expression in cancer cells [23]
Summary
Emerging evidence suggests that microRNAs (miRNAs) are crucially involved in tumorigenesis and that paired expression profiles of miRNAs and mRNAs can be used to identify functional miRNA-target relationships with high precision. No studies have applied integrated analysis to miRNA and mRNA profiles in chordomas. Slow-growing, primary malignant neoplasms of the axial skeleton and arise from the remnant notochord [1,2,3], and surgery remains the best standard treatment [3,4]. These tumors are difficult to be eradicated because they are often adjacent to vital structures. No studies have applied integrated analysis techniques, which can be used to identify functional miRNA-target relationships with high precision to miRNA and mRNA profiles for chordomas
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