碳水化合物磺基转移酶4抑制乙型肝炎病毒相关的肝细胞癌的

StephenW

Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors
Longshan Zhang  1 , Yao Fan  2 , Xiaoqing Wang  1 , Mi Yang  1 , XiXi Wu  1 , Weiqiang Huang  1 , Jin Lan  3 , Liwei Liao  1 , Wenqi Huang  1 , Lu Yuan  1 , Hua Pan  1 , Yuting Wu  1 , Longhua Chen  1 , Jian Guan  1
Affiliations
Affiliations

    1
    Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
    2
    Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, China.
    3
    Department of General Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.

    PMID: 33178582 PMCID: PMC7593664 DOI: 10.3389/fonc.2020.554331

Abstract

Carbohydrate sulfotransferase 4 (CHST4) plays an important role in lymphocyte homing and is abnormally expressed in several cancer types; however, its precise function in tumor development and progression is unknown. Here we confirm that CHST4 is aberrantly expressed in various tumor subtypes. In particular, we found that CHST4 expression was downregulated in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) tumors compared to paired normal tissue. We also showed that CHST4 overexpression inhibited the proliferation and metastasis of HCC cells in vitro. Clinically, CHST4 was identified as an independent prognostic factor for HBV-HCC patients. We further illuminated the anti-tumor role and mechanism of CHST4 in HBV-HCC by constructing a FENDRR-miR-10b-5p-CHST4 competing endogenous RNA network. We found that downregulation of CHST4 expression may promote HBV expression and regulate ribonucleoprotein complex biogenesis to promote malignant behaviors in HBV-HCC. CHST4 may also recruit CD4+ T cells, macrophages, dendritic cells, and neutrophils into the tumor microenvironment to inhibit the progression of HBV-HCC. Overall, our findings suggest that CHST4 acts as a tumor suppressor in HCC-HBV and represents a potential diagnostic and therapeutic target.

Keywords: CHST4; HBV-related hepatocellular carcinoma; competing endogenous RNA; expression profiling; prognostic biomarker.

Copyright © 2020 Zhang, Fan, Wang, Yang, Wu, Huang, Lan, Liao, Huang, Yuan, Pan, Wu, Chen and Guan.

StephenW

碳水化合物磺基转移酶4抑制乙型肝炎病毒相关的肝细胞癌的进展，是几种肿瘤的潜在预后标志物。
张龙山1，姚凡2，王小青1，杨密1，吴喜喜1，黄伟强1，金兰3，廖立伟1，黄文奇1，鹿原1，花潘1，吴雨婷1，陈龙华1，健冠1
隶属关系
隶属关系

    1个
    南方医科大学附属南方医院放疗科，广州
    2
    河北医科大学附属第一医院肿瘤科，石家庄
    3
    南方医科大学附属第三医院普通外科，广州

    PMID：33178582 PMCID：PMC7593664 DOI：10.3389 / fonc.2020.554331

抽象

碳水化合物磺基转移酶4（CHST4）在淋巴细胞归巢中起重要作用，并在几种癌症类型中异常表达。然而，其在肿瘤发展和进展中的确切功能尚不清楚。在这里，我们确认CHST4在各种肿瘤亚型中异常表达。特别是，我们发现与配对的正常组织相比，在乙型肝炎病毒相关的肝细胞癌（HBV-HCC）肿瘤中CHST4表达下调。我们还表明，CHST4的过表达在体外抑制了HCC细胞的增殖和转移。临床上，CHST4被确定为HBV-HCC患者的独立预后因素。通过构建FENDRR-miR-10b-5p-CHST4竞争性内源RNA网络，我们进一步阐明了CHST4在HBV-HCC中的抗肿瘤作用和机制。我们发现，CHST4表达的下调可能促进HBV表达并调节核糖核蛋白复合物的生物发生，从而促进HBV-HCC的恶性行为。 CHST4还可将CD4 + T细胞，巨噬细胞，树突状细胞和嗜中性粒细胞募集到肿瘤微环境中，以抑制HBV-HCC的进展。总的来说，我们的发现表明CHST4在HCC-HBV中起着抑癌作用，并代表了潜在的诊断和治疗靶标。

关键字：CHST4； HBV相关的肝细胞癌；竞争性内源RNA；表达分析预后生物标志物。

版权所有©2020张凡，王，杨，吴，黄，兰，辽，黄，元，潘，吴，陈和关。

StephenW

https://www.frontiersin.org/articles/10.3389/fonc.2020.554331/pdf