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环状RNA介导的竞争性内源性RNA网络在宫颈癌发生发展中的鉴定

Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer.

作者信息

Lou Shaosheng, Yang Wang, Zhao Qian, Ouyang Yunshan, Cao Lingling, Lin Chen

机构信息

Department of Pathology, School of Basic Medical Sciences, Xinjiang Medical University/Key Laboratory of Molecular Biology of Endemic Diseases, Xinjiang, 830000, China.

Department of Pathology, School of Basic Medical Sciences, Xinjiang Medical University/Key Laboratory of Molecular Biology of Endemic Diseases, Xinjiang, 830000, China.

出版信息

Mol Cell Probes. 2024 Dec;78:101984. doi: 10.1016/j.mcp.2024.101984. Epub 2024 Oct 10.

DOI:10.1016/j.mcp.2024.101984
PMID:39307294
Abstract

BACKGROUND

The abnormal expression of circRNA may contribute to the progression of cervical cancer by influencing the biological processes.

AIM

This study aimed to identify the differentially expressed circRNAs in cervical cancer and validate the circ_0008193 ceRNA network in cervical cancer cells.

METHODS

Using the absolute log2 value of fold change >1 and p-value of <0.05, the differentially expressed circRNAs were obtained from GSE102686 and GSE113696 from cervical cancer tissues and cervical cancer cells with the help of the GEO2R tool. Downstream miRNAs and mRNAs were predicted using relevant informatics databases. The circRNA-miRNA-mRNA interaction network was conducted with the assistance of Cytoscape. Circ_0008193-miR-182-5p-PTEN axis was validated with expression level and cell function using RT-qPCR, a dual-luciferase reporter assay, and cellular experiments.

RESULTS

GSE102686 and GSE113696 databases overlapped 7 differentially expressed circRNAs and five circRNAs have the same expression pattern. Based on the literature and expression pattern, a circRNA-miRNA-mRNA network was conducted. The circ_0008193, miR-182-5p, and PTEN expression patterns were downregulation, upregulation, and downregulation, respectively. Overexpressed circ_0008193 suppressed proliferation, migration, and invasion of cervical cancer cells. MiR-182-5p diminished the inhibitory influence of circ_0008193 on cellular behaviors, while PTEN counteracted the effect of miR-182-5p.

CONCLUSION

This investigation revealed the existence of a circRNA-miRNA-mRNA network in cervical cancer, and preliminary verified the function of circ_0008193-miR-182-5p-PTEN axis in cervical cancer cells, which offers additional guidance on investigating the molecular mechanisms of cervical cancer.

摘要

背景

环状RNA(circRNA)的异常表达可能通过影响生物学过程促进宫颈癌的进展。

目的

本研究旨在鉴定宫颈癌中差异表达的circRNA,并验证circ_0008193在宫颈癌细胞中的ceRNA网络。

方法

借助GEO2R工具,使用变化倍数的绝对log2值>1且p值<0.05,从宫颈癌组织和宫颈癌细胞的GSE102686和GSE113696中获得差异表达的circRNA。使用相关信息学数据库预测下游的微小RNA(miRNA)和信使核糖核酸(mRNA)。在Cytoscape的协助下构建circRNA-miRNA-mRNA相互作用网络。使用逆转录定量聚合酶链反应(RT-qPCR)、双荧光素酶报告基因检测和细胞实验,通过表达水平和细胞功能验证circ_0008193-miR-182-5p-PTEN轴。

结果

GSE102686和GSE113696数据库重叠了7个差异表达的circRNA,其中5个circRNA具有相同的表达模式。基于文献和表达模式,构建了circRNA-miRNA-mRNA网络。circ_0008193、miR-182-5p和PTEN的表达模式分别为下调、上调和下调。过表达的circ_0008193抑制宫颈癌细胞的增殖、迁移和侵袭。miR-182-5p减弱了circ_0008193对细胞行为的抑制作用,而PTEN抵消了miR-182-5p的作用。

结论

本研究揭示了宫颈癌中存在circRNA-miRNA-mRNA网络,并初步验证了circ_0008193-miR-182-5p-PTEN轴在宫颈癌细胞中的功能,为研究宫颈癌的分子机制提供了新的指导。

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