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沉默的长链非编码RNA DDX11-AS1或上调的微小RNA-34a-3p通过抑制TRAF5来抑制肝癌细胞的恶性表型。

Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5.

作者信息

Ding Gangqiang, Zeng Yanli, Yang Dongqiang, Zhang Can, Mao Chongshan, Xiao Erhui, Kang Yi, Shang Jia

机构信息

Department of Infectious Diseases, Henan Key Laboratory for Liver Disease, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

出版信息

Cancer Cell Int. 2021 Mar 22;21(1):179. doi: 10.1186/s12935-021-01847-6.

DOI:10.1186/s12935-021-01847-6
PMID:33752668
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7983398/
Abstract

BACKGROUND

Studies have discussed long noncoding RNA DDX11-AS1 (DDX11-AS1)-mediated downstream mechanism in hepatocellular carcinoma (HCC). The goal of this study was to investigate the regulatory mechanism of DDX11-AS1-mediated microRNA-34a-3p (miR-34a-3p)/tumor necrosis factor receptor-associated factor 5 (TRAF5) axis on HCC cells.

METHODS

DDX11-AS1, miR-34a-3p and TRAF5 expression levels in HCC were detected. The correlation of DDX11-AS1, miR-34a-3p and TRAF5 in HCC patients was analyzed by Pearson test. HCC cells were transfected with corresponding plasmid/oligonucleotide, and cell proliferation, migration, invasion, apoptosis and tumor formation ability were detected. Bioinformatics software, dual luciferase report experiment and RNA-pull down experiment analysis were applied to verify the targeting relationship between DDX11-AS1, miR-34a-3p and TRAF5.

RESULTS

Elevated DDX11-AS1 and TRAF5 and reduced miR-34a-3p exhibited in HCC. Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibited the proliferation, migration, invasion, promoted apoptosis of HCC cells and repressed the tumor growth in nude mice. In addition, DDX11-AS1 bound to miR-34a-3p to target TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated up-regulated DDX11-AS1-mediated promotion of tumor growth.

CONCLUSION

Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibits HCC cell growth via elevation of TRAF5, which could be of great benefit to find early diagnostic markers for HCC patients.

摘要

背景

已有研究探讨了长链非编码RNA DDX11-AS1(DDX11-AS1)在肝细胞癌(HCC)中的下游调控机制。本研究旨在探究DDX11-AS1介导的微小RNA-34a-3p(miR-34a-3p)/肿瘤坏死因子受体相关因子5(TRAF5)轴对HCC细胞的调控机制。

方法

检测HCC中DDX11-AS1、miR-34a-3p和TRAF5的表达水平。采用Pearson检验分析HCC患者中DDX11-AS1、miR-34a-3p和TRAF5的相关性。用相应的质粒/寡核苷酸转染HCC细胞,检测细胞的增殖、迁移、侵袭、凋亡及肿瘤形成能力。应用生物信息学软件、双荧光素酶报告实验和RNA下拉实验分析来验证DDX11-AS1、miR-34a-3p和TRAF5之间的靶向关系。

结果

HCC中DDX11-AS1和TRAF5表达升高,miR-34a-3p表达降低。沉默DDX11-AS1或上调miR-34a-3p可抑制HCC细胞的增殖、迁移、侵袭,促进细胞凋亡,并抑制裸鼠肿瘤生长。此外,DDX11-AS1与miR-34a-3p结合靶向TRAF5。沉默TRAF5或提高miR-34a-3p表达可减轻DDX11-AS1上调介导的肿瘤生长促进作用。

结论

沉默DDX11-AS1或上调miR-34a-3p可通过提高TRAF5水平抑制HCC细胞生长,这可能有助于寻找HCC患者的早期诊断标志物。

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