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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
CircXPO1 Promotes Glioblastoma Malignancy by Sponging miR-7-5p
Xuehui Wang1, Jiaying Wang1, Zihui An1
1Key Laboratory of Organ Development and Regeneration of Zhejiang Province, College of Life and Environment Sciences, Hangzhou Normal University, Hangzhou 311121, China.
Abstract:
Mounting evidence suggests that circular RNAs play important roles in the development and progression of cancers. However, their function in glioblastomas (GBM) is still unclear. By circRNA array analysis, we found that circXPO1 (hsa_circ_102737) was significantly upregulated in GBM, and qPCR analysis verified that the circXPO1 expression level was increased in both GBM tissues and cell lines. Functional studies demonstrated that the knockdown of circXPO1 in GBM cell lines repressed cell proliferation and migration; conversely, the overexpression of circXPO1 promoted the malignancy of GBM cells. In line with these findings, circXPO1 inhibition effectively suppressed gliomagenesis in the in situ transplantation model of nude mice. Through bioinformatic analyses and dual-luciferase reporter assays, we showed that circXPO1 directly bound to miR-7-5p, which acted as a tumor suppressor through the negative regulation of RAF1. In conclusion, our studies suggest that the circXPO1/miR-7-5p/RAF1 axis promotes brain tumor formation and may be a potential therapeutic target for GBM treatment.
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