MicroRNA-203 Modulates the Radiation Sensitivity of Human Malignant Glioma Cells

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• 作者：Ji Hyun Chang ; MD^&lowast ; ; Yeo Hyun Hwang ; PhD^&dagger ; ; David J. Lee^&dagger ; ; Dan Hyo Kim ; MS^&dagger ; ; Ji Min Park^&dagger ; ; Hong-Gyun Wu ; MD ; PhD^&lowast ; ; In Ah Kim ; MD ; PhD^&lowast ; ; ^&dagger ; ; ^&Dagger ; ; ^{inah228@snu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：94
• 期：2
• 页码：412-420
• 全文大小：1718 K

文摘

We investigated whether miR-203 could modulate the radiation sensitivity of glioblastoma (GBM) cells and which target gene(s) could be involved.

Methods and Materials

Three human malignant glioma (MG) cell lines and normal human astrocytes were transfected with control microRNA, pre-miR-203, or antisense miR-203. Real-time PCR (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

Overexpression of miR-203 increased the radiation sensitivity of all 3 human MG cell lines and prolonged radiation-induced γ-H2AX foci formation. Bioinformatics analyses suggested that miR-203 could be involved in post-transcriptional control of DNA repair, PI3K/AKT, SRC, and JAK/STAT3 and the vascular signaling pathway. Western blot analysis validated the fact that miR-203 downregulated ATM, RAD51, SRC, PLD2, PI3K-AKT, JAK-STAT3, VEGF, HIF-1α, and MMP2. Overexpression of miR-203 inhibited 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 radiation sensitivity in MG cells by inhibiting DNA damage repair, prosurvival signaling, and epithelium-mesenchyme transition. Taken together, these findings demonstrate that miR-203 could be a target for overcoming the radiation resistance of GBM.