Comprehensive transcriptome mining for biomarkers of radiation sensitivity in breast cancer cells specific focus on circular RNA regulated networks

    Research output


    Radiotherapy is the standard of care for breast cancer. However, surviving radioresistant cells can repopulate following treatment and provoke relapse. Better understanding of the molecular mechanisms of radiation resistance may help improve treatment of radioresistant tumors. To emulate radiation therapy at the cellular level, we exposed MCF7 breast cancer cells to daily radiation doses of 2 Gy up to an accumulated dose of 20 Gy. Fractionally irradiated cells (FIR20) displayed increased clonogenic survival and population doubling time as compared to age-matched sham-irradiated cells and untreated parental MCF7 cells. RNA-sequencing revealed a core signature of 229 mRNAs and 7 circular RNAs of which the expression was significantly altered in FIR20 cells. Dysregulation of several top genes was mirrored at the protein level. The FIR20 cell transcriptome overlapped significantly with canonical radiation response signatures and demonstrated a remarkable commonality with radiation and endocrine therapy resistance expression profiles, suggesting crosstalk between both acquired resistance pathways, as indicated by reduced sensitivity to tamoxifen cytotoxicity of FIR20 cells. Using predictive analyses and functional enrichment, we identified a gene-regulatory network that promotes stemness and inflammatory signaling in FIR20 cells. We propose that these phenotypic traits render breast cancer cells more radioresistant but may at the same time serve as potential targets for combination therapies
    Original languageEnglish
    QualificationMaster of Science
    Awarding Institution
    • University of Antwerp
    • Quintens, Roel, SCK CEN Mentor
    • De Vos, Winnok H., Supervisor, External person
    • Laukens, Kris, Supervisor, External person
    Date of Award8 Nov 2022
    StatePublished - 8 Nov 2022

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