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

Karina Galoian, T. Guettouche, B. Issac, L. Navarro, H. Thomas Temple

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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 epimiRNAs 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.

Original languageEnglish
Pages (from-to)483-492
Number of pages10
JournalTumor Biology
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2014

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Keywords

  • Chondrocytes
  • Chondrosarcoma
  • IGFR
  • MiRNA
  • Notch
  • Sarcomagenesis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Galoian, K., Guettouche, T., Issac, B., Navarro, L., & Thomas Temple, H. (2014). Lost miRNA surveillance of Notch, IGFR pathway-road to sarcomagenesis. Tumor Biology, 35(1), 483-492. https://doi.org/10.1007/s13277-013-1068-5