乙型肝炎病毒相关的肝细胞癌和肝癌干细胞

StephenW

Genes (Basel). 2018 Mar 2;9(3). pii: E137. doi: 10.3390/genes9030137.
Hepatitis B Virus-Associated Hepatocellular Carcinoma and Hepatic Cancer Stem Cells.Mani SKK1, Andrisani O2.
Author information1Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. [email protected].2Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. [email protected].

AbstractChronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. Despite the availability of a HBV vaccine, current treatments for HCC are inadequate. Globally, 257 million people are chronic HBV carriers, and children born from HBV-infected mothers become chronic carriers, destined to develop liver cancer. Thus, new therapeutic approaches are needed to target essential pathways involved in HCC pathogenesis. Accumulating evidence supports existence of hepatic cancer stem cells (hCSCs), which contribute to chemotherapy resistance and cancer recurrence after treatment or surgery. Understanding how hCSCs form will enable development of therapeutic strategies to prevent their formation. Recent studies have identified an epigenetic mechanism involving the downregulation of the chromatin modifying Polycomb Repressive Complex 2 (PRC2) during HBV infection, which results in re-expression of hCSC marker genes in infected hepatocytes and HBV-associated liver tumors. However, the genesis of hCSCs requires, in addition to the expression of hCSC markers cellular changes, rewiring of metabolism, cell survival, escape from programmed cell death, and immune evasion. How these changes occur in chronically HBV-infected hepatocytes is not yet understood. In this review, we will present the basics about HBV infection and hepatocarcinogenesis. Next, we will discuss studies describing the mutational landscape of liver cancers and how epigenetic mechanisms likely orchestrate cellular reprograming of hepatocytes to enable formation of hCSCs.


KEYWORDS: Epigenetics; Epithelial Cell Adhesion Molecule (EpCAM); Hepatitis B Virus (HBV); Hepatocellular Carcinoma (HCC); Hox transcript antisense RNA (HOTAIR); Polycomb Repressive Complex 2 (PRC2); hepatic Cancer Stem Cells (hCSCs); p68/DDX5 RNA helicase; pluripotency genes

PMID:29498629DOI:10.3390/genes9030137

StephenW

基因（巴塞尔）。 2018年3月2日; 9（3）。 pii：E137。 doi：10.3390 / genes9030137。
乙型肝炎病毒相关的肝细胞癌和肝癌干细胞。
Mani SKK1，Andrisani O2。
作者信息

1
    美国印第安纳州西拉法叶普渡大学基础医学部和普渡大学癌症研究中心。 [email protected]。
2
    美国印第安纳州西拉法叶普渡大学基础医学部和普渡大学癌症研究中心。 [email protected]。

抽象

慢性乙型肝炎病毒（HBV）感染与肝细胞癌（HCC）发病机制有关。尽管可以使用乙肝疫苗，但目前对HCC的治疗不足。从全球来看，2.57亿人是慢性HBV携带者，HBV感染母亲所生的孩子成为慢性携带者，注定要患上肝癌。因此，需要新的治疗方法来靶向涉及HCC发病机制的基本途径。越来越多的证据支持肝癌干细胞（hCSCs）的存在，它们在治疗或手术后有助于化疗耐药性和癌症复发。了解hCSCs如何形成将有助于制定治疗策略以防止其形成。最近的研究已经发现了一种表观遗传机制，涉及HBV感染期间染色质修饰多梳抑制复合物2（PRC2）的下调，其导致感染的肝细胞和HBV相关的肝肿瘤中的hCSC标记基因的重新表达。然而，除了hCSC标志物的表达以外，hCSC的发生还需要细胞改变，新陈代谢的重新接线，细胞存活，脱离程序性细胞死亡和免疫逃避。如何在慢性HBV感染的肝细胞中发生这些变化尚不清楚。在这篇综述中，我们将介绍有关HBV感染和肝癌发生的基础知识。接下来，我们将讨论描述肝癌突变景观的研究以及表观遗传机制如何协调肝细胞的细胞重编程以形成hCSC。
关键词：

表观遗传学;上皮细胞粘附分子（EpCAM）;乙型肝炎病毒（HBV）;肝细胞癌（HCC）; Hox转录物反义RNA（HOTAIR）;多梳抑制复合物2（PRC2）;肝癌干细胞（hCSCs）; p68 / DDX5 RNA解旋酶;多能性基因

结论：
    29498629
DOI：
    10.3390 / genes9030137

antiHBVren

研究者的文章先赞一下；

这句话总感觉作者不严谨：
从全球来看，2.57亿人是慢性HBV携带者，HBV感染母亲所生的孩子成为慢性携带者，注定要患上肝癌。

StephenW

回复 antiHBVren 的帖子

同意，“注定发展” 过分武断.