biostudies-literatureInalegwu ASCK CEN Belgian Nuclear Research Centre3410-3435https://www.ebi.ac.uk/biostudies/studies/S-EPMC9533694biostudies-literatureUnknown16(19)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 to improve treatment of radioresistant tumours. 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 with 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 topMolecular oncologyFractionated irradiation of MCF7 breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype.PMC9533694Aspirant Wetenschappelijk Medewerker programmeQuintens RCuypers BBaatout SClaesen JCoolkens AInalegwu AJanssen ADe Vos WHLaukens KfalseFractionated irradiation of MCF7 breast cancer cells rewires a gene regulatory circuit towards a treatment-resistant stemness phenotype.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 to improve treatment of radioresistant tumours. 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 with 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 top2022-01-01T00:00:00Z2022 Oct2025-04-04T23:20:32.845Z2025-04-04T23:20:32.845ZS-EPMC95336943557985210.1002/1878-0261.13226