Down-regulation of MARCO associates with tumor progression in hepatocellular carcinoma
Down-regulation of MARCO associates with tumor progression in hepatocellular carcinoma
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MARCO 的下调与肝细胞癌的肿瘤进展相关
DOI：
10.1016/j.yexcr.2019.111542
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发表时间：
2019
影响因子：
3.7
通讯作者：
Liu Quanyan
中科院分区：
文献类型：
--
作者：
Xiao Yusha;Chen Baiyang;Yang Kang;Wang Quanxiong;Liu Pengpeng;Gu Yang;Zhong Qiu;Liu Zhisu;He Yueming;Liu Quanyan
肝细胞癌是一种死亡率较高的恶性肿瘤，由于缺乏早期诊断方法和有效的治疗方法，其分子机制错综复杂，目前尚不清楚。本研究探讨具有胶原性结构的巨噬细胞受体(MARCO)在肝癌发生发展中的作用。采用聚合酶链式反应和免疫组织化学(IHC)方法检测Marco在肝癌组织、癌旁组织和6株肝癌细胞系中的表达水平。并对肝癌患者的临床资料进行分析。通过体外和体内的多种功能实验，研究Marco在肝细胞癌进展中的作用。为进一步探讨Marco的生物学功能，进行了生物信息学分析。我们发现Marco在肝细胞癌中表达下调，并与良好的预后相关，而Marco表达上调抑制了肿瘤细胞的迁移和侵袭。此外，Marco的过表达不仅促进了肝癌细胞的凋亡，而且在体内和体外都抑制了细胞的增殖。此外，基因集浓缩分析(GSEA)表明Marco可能与P53信号通路有关，这一预测也在本研究中得到证实。综上所述，我们的研究表明Marco参与了肝细胞癌的进展，可以被定义为一种新的可能的生物标志物以及肝癌的治疗靶点。
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.