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环状RNA circGSE1通过miR-138-5p/波形蛋白促进宫颈癌进展。

Circular RNA circGSE1 Promotes Cervical Cancer Progression Through miR-138-5p/Vimentin.

作者信息

Fan Suzhen, Zhao Shujun, Gao Xiang, Qin Qiaohong, Guo Yan, Yuan Zhongfu, Zhang Min, Liu Qing, Li Hongyu

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Dec 31;13:13371-13386. doi: 10.2147/OTT.S282425. eCollection 2020.

Abstract

BACKGROUND

A growing number of studies have identified that circular RNAs (circRNAs) play a vital role in the progression of various tumors. However, the underlying functions and mechanisms of circRNAs in cervical cancer have not been clarified.

METHODS

qRT-PCR was used to detect the level of in cervical cancer tissues and matched normal tissues. In vitro cell wound healing, transwell migration and invasion assays were employed to assess the effects of circGSE1 on cell mobility. The pull-down, luciferase reporter, RIP and rescue assays were performed to evaluate the interaction between circGSE1and miR-138-5p and the regulation of miR-138-5p on Vimentin.

RESULTS

We found that was significantly higher in cervical cancer tissues than that in matched normal tissues. Further analyses revealed that the level of was positively correlated with tumor differentiation, FIGUREO stage, depth of stromal invasion, lymph node metastasis and infiltration of parauterine organ. Kaplan-Meier survival analysis showed that high circGSE1 predicted worse overall survival and disease-free survival. Down-regulated circGSE1 evidently inhibited cell migration and metastasis of cervical cancer, while up-regulated circGSE1 significantly promoted cell migration and metastasis. The pull-down, luciferase reporter and RIP assays revealed that circGSE1 directly bound to and sponge miR-138-5p. MiR-138-5p inhibited the expression of Vimentin through directly binding to 3'UTR of Vimentin mRNA. In addition, miR-138-5p suppressed cell migration and invasion through inhibiting Vimentin expression, and circGSE1 promoted cell migration and invasion through sponging miR-138-5p and enhancing Vimentin expression.

CONCLUSION

CircGSE1 promotes the progression and may act as a novel diagnostic biomarker for disease progression of cervical cancer.

摘要

背景

越来越多的研究表明,环状RNA(circRNAs)在多种肿瘤的进展中起着至关重要的作用。然而,circRNAs在宫颈癌中的潜在功能和机制尚未阐明。

方法

采用qRT-PCR检测宫颈癌组织及配对正常组织中[此处原文缺失具体检测内容]的水平。体外细胞划痕愈合、Transwell迁移和侵袭实验用于评估circGSE1对细胞迁移能力的影响。进行下拉实验、荧光素酶报告基因实验、RNA免疫沉淀实验(RIP)和拯救实验,以评估circGSE1与miR-138-5p之间的相互作用以及miR-138-5p对波形蛋白(Vimentin)的调控。

结果

我们发现宫颈癌组织中[此处原文缺失具体检测内容]显著高于配对的正常组织。进一步分析表明,[此处原文缺失具体检测内容]的水平与肿瘤分化、国际妇产科联盟(FIGO)分期、间质浸润深度、淋巴结转移及子宫旁器官浸润呈正相关。Kaplan-Meier生存分析显示,高表达的circGSE1预示着总体生存率和无病生存率较差。下调circGSE1明显抑制宫颈癌细胞的迁移和转移,而上调circGSE1则显著促进细胞迁移和转移。下拉实验、荧光素酶报告基因实验和RIP实验表明,circGSE1直接结合并吸附miR-138-5p。miR-138-5p通过直接结合波形蛋白mRNA的3'非翻译区(3'UTR)抑制波形蛋白的表达。此外,miR-138-5p通过抑制波形蛋白表达抑制细胞迁移和侵袭,而circGSE1通过吸附miR-138-5p并增强波形蛋白表达促进细胞迁移和侵袭。

结论

CircGSE1促进宫颈癌进展,可能作为宫颈癌疾病进展的新型诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7606/7781114/1611f5e320aa/OTT-13-13371-g0001.jpg

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