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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The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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Conceptualization and Methodology: Jie Bai and Wenzheng Luo; Formal analysis and Data curation: Wenzheng Luo and Jingliang Cheng; Validation and Investigation: Shanshan Zhao and Jie Bai; Writing - original draft preparation and Writing - review and editing: Shanshan Zhao, Jie Bai and Wenzheng Luo; Approval of final manuscript: all authors.
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Supplementary information
Supplementary Fig. 1
The binding sites between circ_0079593 and miR-516b, miR-324-5p, miR-433, miR-633, and miR-665 were obtained from circinteractome. (PNG 423 kb)
Supplementary Fig. 2
The possible miRNA targets of circ_0079593 and the candidate mRNA targets of miR-324-5p. (A and B) We screened out five possible miRNA targets of circ_0079593, including miR-516b, miR-324-5p, miR-433, miR-633, and miR-665. RT-qPCR was conducted to detect the expression of five miRNAs in glioma cells transfected with si-con or si-circ_0079593. (C and D) Four possible mRNA targets of miR-324-5p were screened out, including LMX1A, XBP1, ITGA9, and NRG2. The mRNA expression of LMX1A, XBP1, ITGA9, and NRG2 was measured by RT-qPCR. *P < 0.05, **P < 0.01, and ***P < 0.001. (PNG 172 kb)
Supplementary Fig. 3
The representative images of Fig. 4. (A) The representative images of colony formation assay in Fig. 4C. (B) The representative images of flow cytometry in Fig. 4F. (C) The representative images of transwell migration assay in Fig. 4I. (D) The representative images of transwell invasion assay in Fig. 4J. (E) The representative images of tube formation assay in Fig. 4K. (PNG 2975 kb)
Supplementary Fig. 4
The representative images of Fig. 6. (A) The representative images of colony formation assay in Fig. 6C. (B) The representative images of flow cytometry in Fig. 6F. (C) The representative images of transwell migration assay in Fig. 6I. (D) The representative images of transwell invasion assay in Fig. 6J. (E) The representative images of tube formation assay in Fig. 6K. (PNG 2345 kb)
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Wang, P., Wang, T., Dong, L. et al. Circular RNA circ_0079593 facilitates glioma development via modulating miR-324-5p/XBP1 axis. Metab Brain Dis 37, 2389–2403 (2022). https://doi.org/10.1007/s11011-022-01040-2
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DOI: https://doi.org/10.1007/s11011-022-01040-2