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

Abstract

Chordoma is a rare aggressive bone tumor arising from remnants of the notochord, and patients with chordoma have a poor prognosis. However, the unique expression profiles of microRNAs (miRNAs/miRs) and their downstream signaling pathways in chordoma remain incompletely characterized. The aim of the present study was to delineate the global miRNA expression profile and associated signaling networks in chordoma. miRNA profiling was performed on chordoma and fetal notochord tissues. Differentially expressed miRNAs in chordoma were analyzed using microarrays with hierarchical clustering analysis. The target genes of the differentially expressed miRNAs were predicted, and Gene Ontology (GO) and pathway analyses were performed for the intersecting genes. A total of 42 miRNAs were significantly dysregulated in chordoma compared with that in fetal nucleus pulposus tissues. The expression of hsa-miR-21-3p, hsa-miR-150-5p, hsa-miR-1290 and hsa-miR-623 were validated using the reverse transcription-quantitative polymerase chain reaction. On the basis of the intersection predicted by three databases (Targetscan, microRNA.org and PITA), 10,292 potential miRNA targets were identified. Bioinformatic analyses suggested that these dysregulated miRNAs and their predicted targets were functions of signaling pathways in cancer, the mitogen-activated protein kinase signaling pathway, regulation of actin cytoskeleton, focal adhesion and endocytosis. In particular, human (hsa-)miR-185-5p was identified as a crucial miRNA in chordoma development via the Wnt signaling pathway. The results of the present study provide a comprehensive expression and functional profile of differentially expressed miRNAs associated with chordoma. This profile may serve as a potential tool for biomarker and therapeutic target identification in patients with chordoma.