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环状RNA circSLC8A1通过靶向miR-214-5p/细胞周期蛋白依赖性激酶27(CDC27)轴抑制胶质瘤细胞的增殖和侵袭。

Circular RNA circSLC8A1 inhibits the proliferation and invasion of glioma cells through targeting the miR-214-5p/CDC27 axis.

作者信息

Zhu Jiabao, Liu Xiaobin, Luan Zhonghua, Xue Wei, Cui Haizheng, Zhang Baochen, Xue Guoqiang

机构信息

Department of Neurosurgery, Yuncheng Central Hospital of Shanxi Medical University, Yuncheng, 044000, China.

Department of Neurosurgery, Shaanxi Provincial People's Hospital, Xi'an, 710068, China.

出版信息

Metab Brain Dis. 2022 Apr;37(4):1015-1023. doi: 10.1007/s11011-022-00915-8. Epub 2022 Jan 31.

Abstract

Circular RNA circSLC8A1 is one of the cancer-related circRNAs that is implicated in various cancers. However, studies focusing on the role of circSLC8A1 in glioma is rare. Here we attempted to evaluate the biological function of circSLC8A1 in glioma and explore the potential mechanism. The relative expression of circSLC8A1, miR-214-5p and CDC27 in tissues and cell lines was determined by qRT-PCR. Cell proliferation and invasion were respectively measured by CCK-8 and transwell assays. Protein level of CDC27 was analyzed by western blot. Luciferase reporter assay was performed to confirm the regulatory interaction of cirRNA-miRNA-mRNA. Lowly expressed circSLC8A1 was observed in both glioma tissues and cell lines. Further biological analyses showed that circSLC8A1 inhibits the cell proliferation and invasion of glioma cells. CircSLC8A1 directly sponged miR-214-5p and inhibited miR-214-5p expression in glioma cells. CDC27 was a direct target of miR-214-5p and could be regulated by miR-214-5p. Moreover, miR-214-5p mimics and CDC27 knockdown reversed the inhibitory effects of circSLC8A1 on cell proliferation and invasion. Taken together, our results demonstrated a tumor suppressive role of circSLC8A1 in glioma through regulation of glioma cells proliferation and invasion. The effects of circSLC8A1 were mediated by miR-214-5p/CDC27 axis. Our study provided a new understanding of the occurrence and development of glioma.

摘要

环状RNA circSLC8A1是与癌症相关的环状RNA之一,与多种癌症有关。然而,关注circSLC8A1在胶质瘤中作用的研究很少。在此,我们试图评估circSLC8A1在胶质瘤中的生物学功能,并探索其潜在机制。通过qRT-PCR检测circSLC8A1、miR-214-5p和CDC27在组织和细胞系中的相对表达。分别通过CCK-8和Transwell实验检测细胞增殖和侵袭能力。通过蛋白质印迹法分析CDC27的蛋白水平。进行荧光素酶报告基因实验以确认circRNA-miRNA-mRNA的调控相互作用。在胶质瘤组织和细胞系中均观察到circSLC8A1低表达。进一步的生物学分析表明,circSLC8A1抑制胶质瘤细胞的增殖和侵袭。circSLC8A1直接吸附miR-214-5p并抑制其在胶质瘤细胞中的表达。CDC27是miR-214-5p的直接靶点,可受miR-214-5p调控。此外,miR-214-5p模拟物和CDC27敲低可逆转circSLC8A1对细胞增殖和侵袭的抑制作用。综上所述,我们的结果表明circSLC8A1通过调节胶质瘤细胞的增殖和侵袭在胶质瘤中发挥肿瘤抑制作用。circSLC8A1的作用是由miR-214-5p/CDC27轴介导的。我们的研究为胶质瘤的发生发展提供了新的认识。

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