title: Integrated miRNA-mRNA analysis revealing the potential roles of miRNAs in chordomas.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedics, Peking University Third Hospital, Haidian, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Long
authors.forename: Liang
authors.initials: L
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Wei
authors.forename: Chuan
authors.initials: C
authors.lastname: Ma
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Shaomin
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Liu
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Liu
mesh_terms: D002817:Chordoma / Q000235:genetics*; D016000:Cluster Analysis; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D009672:Notochord / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger