Wang Pengcheng, Wang Tong, Dong Lei, Xu Zhenkuan, Guo Shouzhong, Chang Chengyue
Department of Neurosurgery, Weifang People's Hospital, No 151 Guangwen Street, Kuiwen district, Weifang, 261000, China.
Department of Neurosurgery, Second Hospital of Shandong University, Jinan, China.
Metab Brain Dis. 2022 Oct;37(7):2389-2403. doi: 10.1007/s11011-022-01040-2. Epub 2022 Jul 6.
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.
胶质瘤是一种常见的脑肿瘤,死亡率很高。环状RNA(circRNA)在肿瘤的发生和发展中起着关键作用。然而,circ_0079593在胶质瘤中的功能和分子基础仍不清楚。采用定量实时PCR(qPCR)和蛋白质免疫印迹法检测circ_0079593、微小RNA-324-5p(miR-324-5p)和X盒结合蛋白1(XBP1)的表达。使用细胞计数试剂盒-8(CCK-8)、集落形成实验、流式细胞术、Transwell实验和管腔形成实验来评估细胞功能。通过检测葡萄糖消耗、乳酸生成和ATP水平来测定糖酵解。通过双荧光素酶报告基因实验和RNA免疫沉淀(RIP)实验验证miR-324-5p与circ_0079593或XBP1之间的结合关系。此外,应用异种移植实验检测体内肿瘤生长情况。胶质瘤中circ_0079593和XBP1水平升高,而miR-324-5p水平降低。沉默circ_0079593可抑制胶质瘤细胞的增殖、迁移、血管生成和糖酵解,并诱导其凋亡。circ_0079593通过螯合miR-324-5p(circ_0079593的靶标之一)加速胶质瘤进展。XBP1是miR-324-5p的靶基因,miR-324-5p通过抑制XBP1减轻胶质瘤的恶性生长。此外,沉默circ_0079593可抑制体内肿瘤生长。circ_0079593通过调节miR-324-5p和下游XBP1基因促进胶质瘤的恶性进展,提示circ_0079593可能是胶质瘤一个有前景的治疗靶点。circ_0079593在胶质瘤中表达上调。circ_0079593缺失可抑制胶质瘤进展。circ_0079593通过miR-324-5p/XBP1轴引发胶质瘤发展。circ_0079593沉默可抑制体内胶质瘤的肿瘤发生。