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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
Circular RNA circ_0079593 facilitates glioma development via modulating miR-324-5p/XBP1 axis
Pengcheng Wang1, Tong Wang1, Lei Dong1
1Department of Neurosurgery, Weifang People's Hospital, No 151 Guangwen Street, Kuiwen district, Weifang, 261000, China.
Abstract:
Glioma is a common brain tumor with high mortality. Circular RNAs (circRNAs) play crucial roles in tumor occurrence and development. However, the function and molecular basis of circ_0079593 in glioma remain unknown. Quantitative real-time PCR (qPCR) and Western blot were used for expression determination of circ_0079593, microRNA-324-5p (miR-324-5p) and X-box binding protein 1 (XBP1). Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell assays, and tube formation assay were employed to evaluate cell functions. Glycolysis was determined via detecting glucose consumption, lactate production and ATP level. The binding relationship between miR-324-5p and circ_0079593 or XBP1 was validated by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Besides, xenograft assay was applied to test tumor growth in vivo. Circ_0079593 and XBP1 levels were elevated, while miR-324-5p level was declined in glioma. Silencing of circ_0079593 restrained proliferation, mobility, angiogenesis and glycolysis and induced apoptosis in glioma cells. Circ_0079593 accelerated glioma progression via sequestering miR-324-5p, one of the targets of circ_0079593. XBP1 was a target gene of miR-324-5p, and miR-324-5p alleviated the malignant growth of glioma by repressing XBP1. Furthermore, silence of circ_0079593 hindered tumor growth in vivo. Circ_0079593 contributed to the malignant evolution of glioma via modulating miR-324-5p and downstream XBP1 gene, suggesting that circ_0079593 might be a promising therapeutic target for glioma. Circ_0079593 was boosted in glioma. Circ_0079593 depletion restrained glioma progression. Circ_0079593 triggered glioma development via miR-324-5p/XBP1 axis. Circ_0079593 silence suppressed glioma tumorigenesis in vivo.
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