S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
MicroRNA-203 modulates the radiosensitivity of human malignant glioma cells
마이크로 RNA-203 이 악성뇌교종세포의 방사선감수성에 미치는 영향
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과 방사선종양학과, 2016. 2. 우홍균.
- Purpose: We investigated whether or not miR-203 could modulate the
radiosensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved.
Materials and Methods: Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. RT-PCR, clonogenic assays, immunofluorescence, and invasion/migration assays were performed. To predict the target(s), bioinformatics
analyses using microRNA target databases were performed.
Results: The overexpression of miR-203 increased the radiosensitivity of all the three human MG cell lines and prolonged the radiation-induced γ-H2AX foci formation. The bioinformatics analyses suggested that miR-203 could be involved in the post-transcriptional control of DNA repair, PI3K/AKT, SRC, JAK/STAT3, and the vascular signaling pathway. The western blot analysis validated that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited the invasion and migration potentials, downregulated SLUG and Vimentin, and upregulated Claudin-1 and ZO1.
Conclusions: These data demonstrate that miR-203 potentially controls DNA damage repair via the PI3K/AKT and JAK/STAT3 pathways and may collectively contribute to the modulation of radiosensitivity in MG cells by inhibiting DNA damage repair, pro-survival signaling, and Epithelial-Mesenchymal Transition.
Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radioresistance of GBM.