N6-Methyladenosine Modification and Prognostic Analysis of UBE2K in Hepatocellular Carcinoma: A Potential Target.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jinhui Guo, Jie Zhao
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引用次数: 0

Abstract

The treatment of hepatocellular carcinoma (HCC) is still relatively lacking, the prognosis is poor, and the potential mechanism of carcinogenesis has not been thoroughly studied. In this study, Ubiquitin-conjugating enzyme E2K (UBE2K) transcript levels in HCC patients were up-regulated in two databases, GEO and TCGA. External validation was performed using Western blot experiments. Compared to normal liver cells, UBE2K was upregulated in HCC cell lines. The survival curve and prognosis model revealed that the expression of UBE2K was of high prognostic value in patients with HCC. Transwell assay, wound healing assay and sphere formation assay were used to evaluate the effects of knockdown and overexpression of UBE2K on HCC cells. Overexpression of UBE2K promoted the invasion, migration and stemness of HCC cells, while knocking down UBE2K attenuated the invasion, migration and stemness of HCC cells. Then, through a series of functional analysis (GO and KEEG), it was found that UBE2K played an important role in mRNA processing. We speculate that UBE2K may be involved in HCC progression through its own N6-methyladenosine modification. We therefore used a global methylation inhibitor (3-deazaadenosine) to treat HCC cells and found a gradient increase in the mRNA level of UBE2K. Collectively, the results suggest that UBE2K may be a promising molecular target for the treatment of HCC.

n6 -甲基腺苷修饰和UBE2K在肝细胞癌中的预后分析:一个潜在的靶点。
目前对肝细胞癌(HCC)的治疗仍相对缺乏,预后较差,对其潜在的癌变机制也没有深入的研究。在本研究中,在GEO和TCGA两个数据库中,HCC患者的泛素偶联酶E2K (UBE2K)转录水平上调。采用Western blot实验进行外部验证。与正常肝细胞相比,UBE2K在HCC细胞系中表达上调。生存曲线和预后模型显示UBE2K表达在HCC患者中具有较高的预后价值。采用Transwell法、创面愈合法和球形成法评价UBE2K基因敲除和过表达对HCC细胞的影响。过表达UBE2K可促进HCC细胞的侵袭、迁移和干细胞性,而敲低UBE2K可减弱HCC细胞的侵袭、迁移和干细胞性。然后,通过一系列功能分析(GO和KEEG),发现UBE2K在mRNA加工中发挥重要作用。我们推测UBE2K可能通过其自身的n6 -甲基腺苷修饰参与HCC的进展。因此,我们使用一种全局甲基化抑制剂(3-去氮腺苷)治疗HCC细胞,发现UBE2K mRNA水平呈梯度升高。总之,这些结果表明UBE2K可能是治疗HCC的一个有希望的分子靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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