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MARCO 的下调与肝细胞癌的肿瘤进展相关。

Down-regulation of MARCO associates with tumor progression in hepatocellular carcinoma.

机构信息

Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Hubei, China.

Department of Urology, Renmin Hospital of Wuhan University, Hubei, China.

出版信息

Exp Cell Res. 2019 Oct 15;383(2):111542. doi: 10.1016/j.yexcr.2019.111542. Epub 2019 Aug 2.

DOI:10.1016/j.yexcr.2019.111542
PMID:31381879
Abstract

Hepatocellular carcinoma(HCC) is a malignant tumor with high mortality due to lack of early diagnostic methods and effective treatments, and the molecular mechanisms are intricate and remain unclear. In the present study, the role of macrophage receptor with collagenous structure (MARCO) in tumor advancement of HCC was investigated. We examined expression level of MARCO in HCC samples, corresponding adjacent nontumor tissues and six hepatoma cell lines by polymerase chain reaction and immunohistochemistry (IHC). Clinical information of HCC patients was also analyzed. The role of MARCO involved in HCC progression via multiple functional experiments in vitro and in vivo was investigated. Bioinformatics analysis was conducted to further explore biological functions of MARCO. We found MARCO was suggestively down-regulated in HCC and associated with favorable prognosis, and MARCO upregulation oppressed tumor cell migration and invasion. Besides, overexpression of MARCO not only promoted apoptosis of hepatoma cells but also suppressed proliferation in vivo and in vitro. Furthermore, gene set enrichment analysis (GSEA) analysis suggested that MARCO may be related to the P53 signaling pathway, and this prediction was confirmed in this study as well. In sum, our study indicated that MARCO was involved in HCC progression and it can be defined as a novel probable biomarker as well as treatment target for HCC.

摘要

肝细胞癌(HCC)是一种死亡率高的恶性肿瘤,由于缺乏早期诊断方法和有效治疗方法,其分子机制复杂且仍不清楚。本研究探讨了巨噬细胞胶原结构受体(MARCO)在 HCC 肿瘤进展中的作用。我们通过聚合酶链反应和免疫组织化学(IHC)检测了 HCC 样本、相应的相邻非肿瘤组织和六种肝癌细胞系中 MARCO 的表达水平。还分析了 HCC 患者的临床信息。通过体外和体内多种功能实验研究了 MARCO 参与 HCC 进展的作用。进行了生物信息学分析以进一步探索 MARCO 的生物学功能。我们发现 MARCO 在 HCC 中呈下调趋势,与预后良好相关,MARCO 上调抑制肿瘤细胞迁移和侵袭。此外,MARCO 的过表达不仅促进肝癌细胞凋亡,而且在体内和体外抑制增殖。此外,基因集富集分析(GSEA)分析表明 MARCO 可能与 P53 信号通路有关,本研究也证实了这一预测。总之,我们的研究表明 MARCO 参与 HCC 的进展,它可以被定义为 HCC 的一个新的可能的生物标志物和治疗靶点。

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