CircCPSF6通过吸收miR-145-5p调节MAP4K4来促进肝细胞癌癌症的进展。

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Fei Lu , Jing Gao , Yang Luo , Wei-Lin Jin , Haiping Wang , Chuan-Xing Li , Xun Li
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引用次数: 0

摘要

背景:circRNAs的异常表达与肝细胞癌(HCC)的进展有关。本研究旨在筛选HCC中的促肿瘤环状RNA(circRNAs),以及circCPSF6表达影响HCC特征的机制。方法:利用高通量测序数据在HCC组织中鉴定circCPSF6,并利用实时定量PCR(qRT-PCR)验证其在肝癌组织和细胞系中的表达。使用CCK-8和Transwell测定来评估circCPSF6对HCC增殖和迁移的影响。使用异种移植物小鼠模型研究了circCPSF6在体内对HCC进展的影响,并在体内和体外验证了circCPS F6在HCC中的意义。使用生物信息学分析鉴定circCPSF6相关的miRNA和mRNA。进行萤光素酶报告子、RNA下拉、荧光原位杂交和RNA免疫沉淀分析,以阐明HCC中circCPSF6的调节轴。结果:CircCPSF6在HCC细胞系和组织中的表达增加,其亲代mRNA的表达与肿瘤严重程度呈正相关,与生存率呈负相关。对HCC细胞系的机制分析表明,circCPSF6敲低可抑制肿瘤发生,过表达可促进肿瘤发生。功能分析显示,circCPSF6通过吸收miR-145-5p作为竞争性内源性RNA介导HCC的发展。此外,这种海绵状突起上调了miR-145-5p靶基因MAP4K4,这是一种经典的促肿瘤基因。结论:我们的发现揭示了一个包括circCPSF6-miR-145-5p-MAP4K4轴的调控网络。该轴的元素是潜在的HCC生物标志物,也是HCC治疗的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CircCPSF6 promotes hepatocellular carcinoma cancer progression by regulating MAP4K4 through sponging miR-145-5p

Background

Aberrant expression of circRNAs is involved in the progression of hepatocellular carcinoma (HCC). This study aimed at screening the pro-tumorigenic circular RNAs (circRNAs) in HCC and the mechanisms of circCPSF6 expression influencing HCC characteristics.

Method

circCPSF6 was identified in HCC tissues using high-throughput sequencing data, and its expression was verified in both HCC tissues and cell lines using quantitative real-time PCR (qRT-PCR). CCK-8 and Transwell assays were used to evaluate the effects of circCPSF6 on HCC proliferation and migration. A xenograft mouse model was used to investigate the effects of circCPSF6 on HCC progression in vivo, and the significance of circCPSF6 in HCC was verified both in vivo and in vitro. circCPSF6-associated miRNAs and mRNAs were identified using bioinformatic analyses. Luciferase reporter, RNA pull-down, Fluorescence in situ hybridization, and RNA immunoprecipitation assays were performed to elucidate the circCPSF6 regulatory axis in HCC.

Result

CircCPSF6 expression was increased in HCC cell lines and tissues, and the expression of its parental mRNA was positively correlated with tumor severity and negatively correlated with survival. Mechanistic analyses of HCC cell lines showed that tumorigenesis was inhibited by circCPSF6 knockdown and promoted by its overexpression. Functional analyses revealed that circCPSF6 mediated HCC development by sponging miR-145-5p as a competing endogenous RNA. Furthermore, this sponging upregulated the miR-145-5p target gene MAP4K4, a classical pro-tumorigenic gene.

Conclusion

Our findings reveal a regulatory network that includes the circCPSF6–miR-145-5p–MAP4K4 axis. Elements of this axis are potential HCC biomarkers, as well as targets for HCC treatment.

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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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