环状 RNA circ_0079593 通过海绵吸附 miR-499a-5p 调控 KPNA2 表达促进神经胶质瘤发展。
Circular RNA circ_0079593 promotes glioma development through regulating KPNA2 expression by sponging miR-499a-5p.
机构信息
Department of Neurosurgery, The Fifth People's Hospital of Jinan City, Jinan, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Jan;24(3):1288-1301. doi: 10.26355/eurrev_202001_20186.
OBJECTIVE
Glioma is a common aggressive cancer and a major public health problem worldwide, with high incidence, recurrence, and mortality. Circular RNA (circRNA) has been reported to be involved in glioma, but the role of circ_0079593 in glioma is still unclear.
MATERIALS AND METHODS
The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the expression levels of circ_0079593, miR-499a-5p, and karyopherin alpha 2 (KPNA2) in glioma tissues or cells. The protein expression level of KPNA2 was assessed by Western blot. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), flow cytometry, and transwell assays were conducted to evaluate proliferation, apoptosis, migration and invasion of glioma cells, respectively. The relationship between miR-499a-5p and circ_0079593 or KPNA2 was analyzed by bioinformatics database and confirmed by Dual-Luciferase reporter analyses, respectively. The effects of circ_0079593 silencing in vivo were measured by a xenograft experiment.
RESULTS
Circ_0079593 and KPNA2 were elevated in glioma tissues and cells. Loss-of functional experiments revealed that knockdown of circ_0079593 hampered the progression of glioma by repressing proliferation, motility and inducing apoptosis in vitro and declining tumor growth in vivo. Similarly, suppression of KPNA2 impeded the process of glioma by inhibiting proliferation, motility and increasing apoptosis. MiR-499a-5p, interacting with KPNA2, was a target gene of circ_0079593. In addition, overexpression of KPNA2 could reverse the effects of circ_0079593 knockdown on proliferation, apoptosis, migration and invasion of glioma cells. Mechanistically, circ_0079593 mediated proliferation, motility and apoptosis of glioma cells by regulating KPNA2 expression via sponging miR-499a-5p.
CONCLUSIONS
Circ_0079593 stimulated the pathological process of glioma via acting as competing endogenous RNA to sponge miR-499a-5p.
目的
神经胶质瘤是一种常见的侵袭性癌症，也是全球主要的公共卫生问题，其发病率、复发率和死亡率均较高。环状 RNA（circRNA）已被报道参与神经胶质瘤的发生，但 circ_0079593 在神经胶质瘤中的作用尚不清楚。
材料与方法
采用实时定量聚合酶链反应（RT-qPCR）检测神经胶质瘤组织或细胞中 circ_0079593、miR-499a-5p 和核孔蛋白α 2（KPNA2）的表达水平。采用 Western blot 检测 KPNA2 的蛋白表达水平。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）、流式细胞术和 Transwell 实验分别评估神经胶质瘤细胞的增殖、凋亡、迁移和侵袭能力。通过生物信息学数据库分析 miR-499a-5p 与 circ_0079593 或 KPNA2 的关系，并分别通过双荧光素酶报告分析进行验证。通过异种移植实验检测 circ_0079593 沉默的体内作用。
结果
circ_0079593 和 KPNA2 在神经胶质瘤组织和细胞中升高。功能丧失实验表明，circ_0079593 沉默通过抑制体外神经胶质瘤的增殖、迁移和诱导凋亡以及体内肿瘤生长来阻碍神经胶质瘤的进展。同样，抑制 KPNA2 通过抑制增殖、迁移和增加凋亡来阻碍神经胶质瘤的进程。miR-499a-5p 与 KPNA2 相互作用，是 circ_0079593 的靶基因。此外，过表达 KPNA2 可逆转 circ_0079593 沉默对神经胶质瘤细胞增殖、凋亡、迁移和侵袭的影响。机制上，circ_0079593 通过海绵吸附 miR-499a-5p 调节 KPNA2 表达来介导神经胶质瘤细胞的增殖、迁移和凋亡。
结论
circ_0079593 通过作为竞争性内源性 RNA 来吸附 miR-499a-5p 来刺激神经胶质瘤的病理过程。
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