Department of Neurosurgery, Tongling People's Hospital, No. 468, Bijiashan Road, Tongling, 244000, Anhui, China.
Neurochem Res. 2020 Dec;45(12):2828-2839. doi: 10.1007/s11064-020-03131-x. Epub 2020 Sep 22.
Glioma is the common type of malignant tumor with high mortality worldwide. Survival rate of patients with glioma remains poor, and almost half of patients died within 15 months. The increasing researches indicated that long non-coding RNA (lncRNA) Zinc finger antisense 1 (ZFAS1) played essential roles in tumor initiation and progression. Therefore, it is worth clarifying potential role of ZFAS1 in glioma. The expression levels of ZFAS1, miR-1271-5p, and Hexokinase 2 (HK2) in glioma tissues and cells were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Kaplan-Meier curve was employed to analyze the relationship between cumulative survival time of glioma patients and expression level of ZFAS1. The cell proliferation, apoptosis, and mobility ability were assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays. The relationship among ZFAS1, miR-1271-5p, and HK2 was analyzed by bioinformatics assay, dual-luciferase reporter and Pearson's correlation analyses. The protein expression level of HK2 was examined by western blot assay. Finally, a xenograft experiment was established to assess the effects of ZFAS1 silencing in vivo. ZFAS1 was highly expressed in glioma tissues and cells, besides, the expression level of ZFAS1 was associated with survival time of glioma patients. Functional experiments suggested that knockdown of ZFAS1 or upregulation of miR-1271-5p constrained proliferation, migration and induced apoptosis of glioma cells. In addition, miR-1271-5p, interacted with HK2, was a target of ZFAS1. The gain of HK2 could overturn ZFAS1 silencing-induced effects on glioma cells. Besides, deficiency of ZFAS1 hindered tumor growth in vivo. ZFAS1 was involved in proliferation, migration, and apoptosis of glioma cells via regulating miR-1271-5p/HK2 axis.
神经胶质瘤是全球常见的高死亡率恶性肿瘤类型。神经胶质瘤患者的存活率仍然较差,几乎一半的患者在 15 个月内死亡。越来越多的研究表明,长非编码 RNA(lncRNA)锌指反义 1(ZFAS1)在肿瘤发生和进展中发挥着重要作用。因此,阐明 ZFAS1 在神经胶质瘤中的潜在作用是值得的。通过实时定量聚合酶链反应(RT-qPCR)检测神经胶质瘤组织和细胞中 ZFAS1、miR-1271-5p 和己糖激酶 2(HK2)的表达水平。采用 Kaplan-Meier 曲线分析神经胶质瘤患者累积生存时间与 ZFAS1 表达水平的关系。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑-3-溴化铵(MTT)、流式细胞术和 Transwell 分析评估细胞增殖、凋亡和迁移能力。通过生物信息学分析、双荧光素酶报告基因和 Pearson 相关分析分析 ZFAS1、miR-1271-5p 和 HK2 之间的关系。通过 Western blot 分析检测 HK2 的蛋白表达水平。最后,建立异种移植实验评估 ZFAS1 沉默在体内的作用。ZFAS1 在神经胶质瘤组织和细胞中高表达,此外,ZFAS1 的表达水平与神经胶质瘤患者的生存时间有关。功能实验表明,ZFAS1 敲低或 miR-1271-5p 上调抑制神经胶质瘤细胞的增殖、迁移并诱导细胞凋亡。此外,miR-1271-5p 与 HK2 相互作用,是 ZFAS1 的靶标。HK2 的获得可以推翻 ZFAS1 沉默对神经胶质瘤细胞的影响。此外,ZFAS1 缺乏可抑制体内肿瘤生长。ZFAS1 通过调节 miR-1271-5p/HK2 轴参与神经胶质瘤细胞的增殖、迁移和凋亡。