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基于生物信息学和实验鉴定 MCM 家族作为肝细胞癌潜在的治疗和预后靶点。

Identification of MCM family as potential therapeutic and prognostic targets for hepatocellular carcinoma based on bioinformatics and experiments.

机构信息

Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

出版信息

Life Sci. 2021 May 1;272:119227. doi: 10.1016/j.lfs.2021.119227. Epub 2021 Feb 16.

Abstract

AIMS

The minichromosome maintenance (MCM) complex is highly conserved, which has drawn increasing attention on physiology and pathology process. However, the role of MCM in hepatocellular carcinoma (HCC) remains largely unclear. We aimed to conduct systematic analysis of expression patterns, prognostic values and potential functions of nine MCM genes in HCC, thus identifying their role in HCC.

MAIN METHODS

In our study, we systemically analyzed the role of MCM in prognosis and HCC progression by several bioinformatics analysis tools. Immunohistochemical (IHC) assays were utilized to valid the protein expression of MCM in HCC and in vitro experiments were used to confirm the functions of MCMs in HCC proliferation.

KEY FINDINGS

Overexpression of MCM2-8 and MCM10 were found to be significantly associated with clinical parameters and poor prognosis of HCC patients. The function of MCM was mainly enriched in DNA replication. Moreover, MCM were also associated with several cancer pathway and drug sensitivity in HCC. Close correlations were observed between immune cell infiltration and MCM in HCC. Cell Counting Kit-8 (CCK-8) and clone formation assays suggested the role of MCM2-8 and MCM10 in HCC proliferation.

SIGNIFICANCE

These results have implied that deregulated MCM played an important role in HCC progression and might be considered as potential therapeutic and prognostic targets for HCC.

摘要

目的

微小染色体维持(MCM)复合物高度保守,这引起了人们对生理学和病理学过程的越来越多的关注。然而,MCM 在肝细胞癌(HCC)中的作用在很大程度上仍不清楚。我们旨在对 9 种 MCM 基因在 HCC 中的表达模式、预后价值和潜在功能进行系统分析,从而确定它们在 HCC 中的作用。

主要方法

在我们的研究中,我们通过几种生物信息学分析工具系统地分析了 MCM 在预后和 HCC 进展中的作用。免疫组织化学(IHC)检测用于验证 MCM 在 HCC 中的蛋白表达,体外实验用于证实 MCM 在 HCC 增殖中的功能。

主要发现

MCM2-8 和 MCM10 的过表达与 HCC 患者的临床参数和不良预后显著相关。MCM 的功能主要富集在 DNA 复制中。此外,MCM 还与 HCC 中的几种癌症途径和药物敏感性相关。在 HCC 中,观察到免疫细胞浸润与 MCM 之间存在密切的相关性。细胞计数试剂盒-8(CCK-8)和克隆形成实验表明 MCM2-8 和 MCM10 在 HCC 增殖中的作用。

意义

这些结果表明,失调的 MCM 在 HCC 进展中起着重要作用,可能被认为是 HCC 的潜在治疗和预后靶点。

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