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环状RNA8924通过竞争性结合miR-518d-5p/519-5p家族并调节CBX8的表达促进宫颈癌细胞的增殖、迁移和侵袭。

CircRNA8924 Promotes Cervical Cancer Cell Proliferation, Migration and Invasion by Competitively Binding to MiR-518d-5p /519-5p Family and Modulating the Expression of CBX8.

作者信息

Liu Jiamei, Wang Danbo, Long Zaiqiu, Liu Jing, Li Weishan

出版信息

Cell Physiol Biochem. 2018;48(1):173-184. doi: 10.1159/000491716. Epub 2018 Jul 13.

Abstract

BACKGROUND/AIMS: Circular RNAs (circRNAs) play a significant role in the development and progression of various human cancers. However, the expression and function of circRNAs in cervical cancer (CC) have rarely been explored. The aim of this study was to investigate the biological function of circRNA8924 in CC and elucidate the possible molecular mechanism involved.

METHODS

Quantitative polymerase chain reaction was used to determine mRNA expression of circRNA8924, miR-518d-5p/519-5p and CBX8 in CC tissues and cells. CBX8 protein expression was measured by Western blotting. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay to determine cell migration and invasion. The luciferase reporter assay was used to determine the direct regulation of miR-518d-5p/519-5p and circRNA8924 or CBX8 Results: The study demonstrated that the expression level of circRNA8924 in CC was significantly higher than that in the adjacent normal tissues (P < 0.001), and that it was also associated with tumor size, FIGO staging and myometrial invasion. The knockdown of circRNA8924 significantly inhibited the proliferation, migration and invasion of CC cells SiHa and HeLa. The expression level of miR-518d-5p/519-5p was negatively correlated with circRNA8924, and circRNA8924 regulated CBX8 by competitively binding to miR-518d-5p/519-5p.

CONCLUSIONS

CircRNA8924 is highly expressed in CC tissue and can be considered a competitive endogenous RNA of the miR-518d-5p/519-5p family to promote the malignant biological behavior of CC cells. It is suggested that it may serve as a new biomarker for CC diagnosis and disease progression and provide potential targets for targeted therapy.

摘要

背景/目的:环状RNA(circRNAs)在多种人类癌症的发生和发展中发挥着重要作用。然而,circRNAs在宫颈癌(CC)中的表达及功能鲜有研究。本研究旨在探讨circRNA8924在CC中的生物学功能,并阐明其可能涉及的分子机制。

方法

采用定量聚合酶链反应检测CC组织和细胞中circRNA8924、miR-518d-5p/519-5p和CBX8的mRNA表达。通过蛋白质免疫印迹法检测CBX8蛋白表达。采用CCK-8法评估细胞增殖,采用Transwell法检测细胞迁移和侵袭能力。采用荧光素酶报告基因检测法确定miR-518d-5p/519-5p与circRNA8924或CBX8之间的直接调控关系。结果:研究表明,circRNA8924在CC中的表达水平显著高于相邻正常组织(P<0.001),且与肿瘤大小、国际妇产科联盟(FIGO)分期及肌层浸润有关。敲低circRNA8924可显著抑制CC细胞SiHa和HeLa的增殖、迁移和侵袭。miR-518d-5p/519-5p的表达水平与circRNA8924呈负相关,且circRNA8924通过竞争性结合miR-518d-5p/519-5p来调控CBX8。

结论

CircRNA8924在CC组织中高表达,可被视为miR-518d-5p/519-5p家族的竞争性内源性RNA,促进CC细胞的恶性生物学行为。提示其可能作为CC诊断和疾病进展的新生物标志物,并为靶向治疗提供潜在靶点。

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