Effects of miR-219 and miR-221on radiosensitivity of glioblastoma cells

Research project within scientific and technological cooperation between Republic of Serbia and Federal Republic of Germany 2021-2022
Principal Investigator: Dr Danijela Stanisavljevic Ninkovic
Participants from IMGGE: Academician Milena Stevanovic, dr Danijela Drakulic, Vanda Balint, Jelena Pejic

Glioblastoma represents the most common and aggressive type of cancer that occurs in brain. The location in the brain makes tumour difficult to treat and prognoses for survival of patients with glioblastoma are poor with high mortality rates. Current therapy for this malignant brain tumour is aggressive, combining surgery, followed by radiotherapy. One of the unwanted and limiting features of glioblastoma is resistance to radiation. Radioresistance (relapse after radiotherapy) is a major challenge for the current radiotherapy. Finding drugs or molecules that can overcome this restrain is crucial for finding novel more effective glioblastoma treatments. MicroRNAs (miRNAs) are a class of small non-coding RNAs that play important roles in regulating gene expression. Emerging evidences suggest that miRNAs play a critical role in the modulation of key cellular pathways that mediate response to radiation, influencing the radiosensitivity of the cancer cells.Various miRNAs can influence several processes that are key characteristics of glioblastoma development, like tumour invasiveness, apoptosis, angiogenesis and proliferation. Evolutionary conserved miR-219 has specific expression in brain and its overexpression in glioblastomacan decrease proliferation, migration and invasion acting as tumour suppressor. In addition, miR-221 can regulate glioblastoma tumorogenesis by increasing cell migration and cell growth and can served as a therapeutic tool for drug resistance testing or sensitivity to anticancer drugs. The main goal of this proposal is to analyse effects of modulation of miR-219 and miR-221 expressionon radiosensitivity of glioblastoma cells. The results of research will contribute to better understanding how miR-219 and miR-221 affect radiosensitivity of glioblastoma cells
and may lead to improvement of radiotherapy of glioblastoma tumours making progress in treatment of this aggressive and one of the deadliest forms of brain cancer.