Integrated miRNA-mRNA Analysis Revealing the Potential Roles of miRNAs in Chordomas

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.

MicroRNA profiling and bioinformatics analyses reveal the potential roles of microRNAs in chordoma

“…In the present study, the most significant pathways were associated with tumor pathogenesis, including signaling pathways in cancer, MAPK signaling pathway, regulation of actin cytoskeleton, focal adhesion and endocytosis. Consistent with previous studies, the MAPK signaling pathway was the most highly overrepresented genetic pathway (17,18). Additionally, our previous study demonstrated that Raf-1 and extracellular-signal-regulated kinase 1/2, which are important members of the MAPK signaling pathway, were overexpressed in chordoma and associated with tumor progression (19).…”

Low expression of microRNA-1908 predicts a poor prognosis for patients with ovarian cancer

“…Another study identified that the low expression of miR-1908 predicted a poor prognosis in glioma (12). In addition, miR-1908 has also been associated with the prognosis of chordoma, hepatoma and melanoma (13)(14)(15)(16). miR-1908 has different functions in different cancer types, as it may target different genes.…”

The molecular aspects of chordoma

“…Furthermore, 911 of the mRNAs matched up with putative miRNA targets. The MAPK pathway was shown to increase in chordomas in a constant manner through KEGG pathway analysis and downregulation of miR-663a, miR-149-3p, miR-1908, miR-2861, and miR-3185, which might explain the increase in the activity of their corresponding mRNAs in the pathway [53].…”