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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Lost miRNA surveillance of Notch, IGFR pathway--road to sarcomagenesis

K Galoian, T Guettouche, B Issac

    Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
    |August 21, 2013
    PubMed

    Insights

    This study reveals that microRNAs (miRNAs) are crucial in controlling cancer development by regulating key pathways like NOTCH and IGFR. Dysregulation of these miRNAs and their targets, including cancer testis antigens, contributes to sarcomagenesis.

    Area of Science:

    • Molecular Biology
    • Oncology
    • Epigenetics

    Background:

    • Sarcomagenesis involves complex molecular alterations.
    • MicroRNAs (miRNAs) play critical roles in gene regulation and cellular processes.
    • Understanding miRNA deregulation is key to elucidating cancer development.

    Purpose of the Study:

    • To compare differentially expressed miRNAs and their targets in human chondrosarcoma (JJ012) and chondrocyte (C 28) cell lines.
    • To identify signal transduction pathways deregulated in sarcomagenesis.
    • To investigate the role of miRNAs in the regulation of cancer testis antigen (CTA) genes.

    Main Methods:

    • Total RNA extraction and quality assessment.
    • MicroRNA profiling using Exiqon human miRNA panel and Illumina microarray.
    • Target gene prediction using miRWalk database and verification via quantitative reverse transcriptase–PCR.
    • Analysis of NOTCH, IGFR, rat sarcoma, and Src pathway involvement.

    Main Results:

    • Identified 28 significant miRNAs (P value ≤0.01) in chondrosarcoma cells.
    • Predicted 3,045 target genes for these miRNAs.
    • Observed predominant dysregulation of NOTCH, IGFR, rat sarcoma, and Src pathways.
    • Found correlation between upregulated CTA genes and IGFR pathway activity.

    Conclusions:

    • Lost miRNA surveillance of NOTCH and IGFR pathways contributes to sarcomagenesis.
    • Upregulation of CTA genes is linked to hypomethylation controlled by epi-miRNAs.
    • miRNAs may directly regulate epigenetic processes influencing target gene expression.

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