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长链非编码RNA MIR194-2HG通过调控miR-1207-5p/TCF19/ Wnt/β-连环蛋白信号促进肝癌细胞增殖和转移

LncRNA MIR194-2HG Promotes Cell Proliferation and Metastasis via Regulation of miR-1207-5p/TCF19/Wnt/β-Catenin Signaling in Liver Cancer.

作者信息

Xu Guoping, Zhu Yungang, Liu Huijia, Liu Yingying, Zhang Xuening

机构信息

Department of Medical Imaging, The Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China.

Graduate School of Tianjin Medical University, Tianjin Medical University, Tianjin 300070, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Oct 6;13:9887-9899. doi: 10.2147/OTT.S264614. eCollection 2020.

Abstract

PURPOSE

LncRNAs play an important role in tumorigenesis and cancer progression in liver cancer. Although many lncRNAs have been reported, the role of MIR194-2HG and the underlying mechanism mediated by it are still largely unknown in HCC. This study aimed to investigate the biological role and mechanism of MIR194-2HG in liver cancer.

MATERIALS AND METHODS

The expression of MIR194-2HG was determined in liver cancer tissues and cells by RT-qPCR. The overall survival rate of MIR194-2HG was analyzed by Kaplan-Meier survival analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays were carried out to detect cell migration and invasion. Western blotting was used to quantify the levels of all proteins. The regulatory mechanism of the MIR194-2HG/miR-1207-5p/TCF19 axis in liver cancer was investigated by dual-luciferase activity reporter assay, Kaplan-Meier survival analysis, and Western blotting.

RESULTS

MIR194-2HG was upregulated in liver cancer tissues and cell lines. Liver cancer patients with higher expression of MIR194-2HG revealed poor overall survival compared with those who had lower expression of MIR194-2HG. MIR194-2HG promoted the proliferation, migration, and invasion of HepG2 and Huh7 cells by acting as a ceRNA mechanism for the miR-1207-5p/TCF19 axis to activate the Wnt/β-catenin signaling pathway.

CONCLUSION

MIR194-2HG acts in an oncogenic role and activates the Wnt/β-catenin signaling pathway via a miR-1207-5p/TCF19 axis-mediated mechanism, which provides a novel avenue for diagnostic or therapeutic interventions in liver cancer.

摘要

目的

长链非编码RNA(lncRNAs)在肝癌的肿瘤发生和癌症进展中发挥重要作用。尽管已有许多lncRNAs被报道,但MIR194 - 2HG在肝癌中的作用及其介导的潜在机制仍大多未知。本研究旨在探讨MIR194 - 2HG在肝癌中的生物学作用及机制。

材料与方法

通过逆转录定量聚合酶链反应(RT - qPCR)检测肝癌组织和细胞中MIR194 - 2HG的表达。采用Kaplan - Meier生存分析评估MIR194 - 2HG的总体生存率。进行3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐(MTT)、集落形成和Transwell实验以检测细胞迁移和侵袭。蛋白质免疫印迹法用于定量所有蛋白质的水平。通过双荧光素酶活性报告基因检测、Kaplan - Meier生存分析和蛋白质免疫印迹法研究MIR194 - 2HG/miR - 1207 - 5p/TCF19轴在肝癌中的调控机制。

结果

MIR194 - 2HG在肝癌组织和细胞系中上调。与MIR194 - 2HG低表达的肝癌患者相比,高表达的患者总体生存率较差。MIR194 - 2HG通过作为miR - 1207 - 5p/TCF19轴的竞争性内源RNA(ceRNA)机制来激活Wnt/β - 连环蛋白信号通路,从而促进HepG2和Huh7细胞的增殖、迁移和侵袭。

结论

MIR194 - 2HG发挥致癌作用,并通过miR - 1207 - 5p/TCF19轴介导的机制激活Wnt/β - 连环蛋白信号通路,这为肝癌的诊断或治疗干预提供了一条新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3e8/7547811/022faeee25a4/OTT-13-9887-g0001.jpg

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