MiR-134, Epigenetically Silenced In Gliomas, Could Mitigate The Malignant Phenotype By Targeting KRAS
Z. Wang, C. Zhang, Z. Wang, X. Meng, Xiaojuan Liu, B. Han, Chunbin Duan, J. Cai, Zhong-fei Hao, M. Chen, T. Jiang, Y. Li, C. Jiang, Hong-jun Wang
Published 2018 · Medicine, Biology
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Gliomas are characterized by a malignant phenotype with proliferation, cell cycle arrest and invasion. To explore the biological consequences of epigenetically regulated miRNAs, we performed a microarray-based screening (whose expression was affected by 5-AZA treatment) followed by bisulfite sequencing validation. We found that miR-134 as an epigenetically regulated suppressor gene with prognostic value in gliomas. MicroRNA-134 was downregulated in high-grade gliomas, especially in GBM samples. Functional studies in vitro and in vivo in mouse models showed that overexpression of miR-134 was sufficient to reduce cell cycle arrest, cell proliferation and invasion. Target analysis and functional assays correlated the malignant phenotype with miR-134 target gene KRAS, an established upstream regulator of ERK and AKT pathways. Overall, our results highlighted a role for miR-134 in explaining the malignant phenotype of gliomas and suggested its relevance as a target to develop for early diagnostics and therapy.
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