mir-219 as a potential radiosensitier in glioblastoma cells

Abstract

Glioblastoma (GBM) is the most aggressive type of primary malignant brain tumor, and is characterized by an extremely poor therapeutic response and overall survival. Adjuvant radiotherapy remains the standard treatment after surgical resection. Resistance to radiotherapy is frequently observed in patients with GBM, which limits treatment efficacy. 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 are important regulatory molecules that can control GBM radiosensitivity by affecting radiation-related signal transduction pathways, such as proliferation, migration, senescence, and cell cycle regulation. Evolutionary conserved miR-219 has specific expression in brain and it can act as tumour suppressor in GBM. The main goal of this study is to analyze the effects of modulation of miR-219 expression on radiosensitivity of GBM cells. First, in silico analyses show that the expression of miR-219 is downregulated in GBM tumours and that many of the target genes of this miRNA have a critical role in the modulation of key cellular pathways that mediate response to radiation. Additionally, our results show increased expression of miR-219 upon irradiation of GBM cells. To further investigate the function of mir-219 in GBM radiosensitivity, a stable miR-219- overexpressed LN229 and U87 cell line was constructed using lentivirus transduction. In addition, we analyze the effect of miR-219 overexpression on proliferation and senescence of GBM cells. The results of this research will contribute to better understanding how miR-219 affect radiosensitivity of GBM cells and may lead to improvement of radiotherapy of GBM tumours making progress in treatment of this aggressive and one of the deadliest forms of brain cancer.