Tumor Biology

, Volume 35, Issue 1, pp 483–492

Lost miRNA surveillance of Notch, IGFR pathway—road to sarcomagenesis

  • K. Galoian
  • T. Guettouche
  • B. Issac
  • L. Navarro
  • H. T. Temple
Research Article

DOI: 10.1007/s13277-013-1068-5

Cite this article as:
Galoian, K., Guettouche, T., Issac, B. et al. Tumor Biol. (2014) 35: 483. doi:10.1007/s13277-013-1068-5


The goal of this study was to compare and analyze differentially expressed miRNA and their targets in human chondrosarcoma JJ012 and chondrocytes C 28 cell lines (control) to elucidate deregulation of major signal transduction pathways involved in sarcomagenesis. Total RNA extraction was followed by analyzing RNA quality and integrity. Exiqon human miRNA panel of 743 unique miRNA assays and Illumina microarray HT-12 platform and quantitative reverse transcriptase–PCR verification of targets were performed. The results from human miRNA Exiqon arrays with biological triplicates indicated 28 significant miRNAs (P value ≤0.01). A total 3,045 target genes were derived from the miRWalk database for these 28 miRNAs with 587 common and 2,458 unique target genes. The results of our analyses of the significantly downregulated and upregulated miRNAs in chondrosarcoma cell line indicated the predominant dysregulation of NOTCH, insulin-like growth factor receptor (IGFR), and downstream rat sarcoma, and Src pathways, compared to control. Among the upregulated targets for upregulated miRNAs were the cluster of cancer testis antigen (CTA) genes, located on X chromosome, and their expression was correlated to IGFR pathway activity. Based on our observations, lost miRNA surveillance of NOTCH and IGFR pathways is involved in and leads to sarcomagenesis. We conclude that upregulation of CTA genes is due to hypomethylation that are controlled by epi-miRNAs. We do not preclude the possibility that the upregulated miRNAs, which target CTA genes located in adjacent regions in chromosome X, are epi-miRNAs that influence target gene expression by directly regulating epigenetic processes. Future endeavors will be directed towards understanding the posttranscriptional modifications that affect miRNA expression in sarcomas.


Notch IGFR Sarcomagenesis Chondrosarcoma miRNA Chondrocytes 

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • K. Galoian
    • 1
  • T. Guettouche
    • 2
  • B. Issac
    • 3
  • L. Navarro
    • 4
  • H. T. Temple
    • 5
  1. 1.Department of Orthopaedic Surgery, Miller School of MedicineUniversity of MiamiMiamiUSA
  2. 2.Children’s Hospital of PhiladelphiaCenter for Applied GenomicsPhiladelphiaUSA
  3. 3.Biostatistics and Bioinformatics Core/Division of Bioinformatics, Sylvester Comprehensive Cancer CenterUniversity of MiamiMiamiUSA
  4. 4.Oncogenomics Core, Sylvester Cancer CenterUniversity of MiamiMiamiUSA
  5. 5.Department of Orthopaedic Surgery and University of Miami Tissue Bank Division, Miller School of MedicineUniversity of MiamiMiamiUSA

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