CREB1-induced miR-1204 promoted malignant phenotype of glioblastoma through targeting NR3C2

CREB1 诱导的 miR-1204 通过靶向 NR3C2 促进胶质母细胞瘤的恶性表型

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作者:Xinli Zhao #, Fazheng Shen #, Jiwei Ma, Shupeng Zhao, Lei Meng, Xiangyang Wang, Shufeng Liang, Jianing Liang, Chaoshuai Hu, Xinzhong Zhang

Background

Glioblastoma (GBM) is a subclass of brain malignancy with unsatisfactory prognosis. MicroRNAs (miRNAs) are a group of non-coding RNAs (ncRNAs) that exert key function on tumorigenesis and tumor development. Purposes: The

Conclusions

We observed for the first time that CREB1-induced miR-1204 promoted malignant phenotype of GBM through targeting NR3C2, indicating that miR-1204 acted as a novel oncogenic miRNA in GBM.

Methods

Expressions of miR-1204, NR3C2 and CREB1 were detected by RT-qPCR and western blot. Proliferation and apoptosis of GBM cells were detected by CCK-8, colony formation, caspase-3 activity and TUNEL assays. Molecular interplays were examined by ChIP, RIP, and luciferase reporter assays.

Results

MiR-1204 level was elevated in GBM cell lines. Functionally, miR-1204 aggravated cell proliferation whereas suppressed cell apoptosis in GBM cells. Mechanistically, cAMP Responsive Element Binding Protein 1 (CREB1) bound to the promoter of miR-1204 and activated the transcription of miR-1204. Furthermore, miR-1204 targeted and inhibited Nuclear receptor subfamily 3 group C member 2 (NR3C2), a tumor suppressor gene in GBM cells. Rescue assays indicated that NR3C2 participated in the regulation of miR-1204 on the malignant phenotype of GBM cells. Conclusions: We observed for the first time that CREB1-induced miR-1204 promoted malignant phenotype of GBM through targeting NR3C2, indicating that miR-1204 acted as a novel oncogenic miRNA in GBM.

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