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Published on: October 4, 2019
Integrated miRNA-mRNA analysis revealing the potential roles of miRNAs in chordomas
Cheng Long1, Liang Jiang, Feng Wei
1Department of Orthopedics, Peking University Third Hospital, Haidian, Beijing, China.
Introduction:
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. 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.
Methods:
Differentially 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.
Results:
The 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.
Conclusion:
This 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.
Insights
This study reveals key microRNA (miRNA) and mRNA expression profiles in chordomas, highlighting the MAPK and Notch pathways
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- MicroRNAs (miRNAs) are implicated in tumorigenesis, with paired miRNA and mRNA expression profiles aiding in identifying functional miRNA-target relationships.
- Integrated analysis of miRNA and mRNA profiles has not been previously applied to chordomas, a rare bone tumor.
Purpose of the Study:
- To investigate the pathogenesis of chordomas by performing an integrated analysis of miRNA and mRNA expression profiles.
- To identify key molecular pathways and miRNA-target interactions involved in chordoma development.
Main Methods:
- Microarray analysis was used to identify differentially expressed miRNAs and mRNAs in chordoma tissues compared to notochord tissues.
- Hierarchical clustering, miRNA target prediction, and overlap analysis with differentially expressed mRNAs were performed.
- Gene Ontology (GO) and pathway analyses were conducted on intersecting genes.
Main Results:
- 33 miRNAs and 2,791 mRNAs were significantly dysregulated in chordomas.
- 911 mRNAs overlapped with predicted miRNA target genes.
- The MAPK pathway was enriched in chordoma tissues, with specific miRNAs (miR-149-3p, miR-663a, miR-1908, miR-2861, miR-3185) potentially regulating it. The Notch signaling pathway and impaired notochord calcification/ossification were also implicated.
Conclusions:
- This study provides an integrated miRNA and mRNA dataset for chordomas.
- The MAPK and Notch signaling pathways, along with related miRNAs, are likely involved in chordoma pathogenesis.
- Chordoma occurrence may be linked to dysfunctional notochord calcification or ossification.
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