抗病毒治疗可能会降低HBx，从而影响肝癌发生中的cccDNA和MSL2

StephenW

Oncol Lett. 2019 Nov;18(5):4984-4991. doi: 10.3892/ol.2019.10833. Epub 2019 Sep 10.
Antiviral therapy may decrease HBx, affecting cccDNA and MSL2 in hepatocarcinogenesis.
Jin XL1, Hong SK1, Kim H1, Lee SK1, Yi NJ1, Lee KW1, Suh KS1.
Author information

1
    Department of Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Abstract

Chronic hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) is an intermediate in the life cycle of HBV. HBV-encoded X protein (HBx), a key viral oncoprotein, can be specifically ubiquitylated by male specific lethal 2 (MSL2), which causes upregulation of HBx activity and promotes transcription, cell proliferation and tumor growth. The present study compared the levels of cccDNA, MSL2 mRNA and HBx mRNA in tumor and peri-tumor tissues, and clarified the effect of antiviral therapy on these indicators. Levels of intrahepatic cccDNA, MSL2 mRNA and HBx mRNA were determined using quantitative PCR in patients with HBV-associated HCC who had undergone liver surgery. A total of 50 patients were included in the present study. Prior to surgery, 31 patients had undergone antiviral treatment. Intrahepatic cccDNA levels were significantly higher in the tumor tissues compared with the peri-tumor tissues (P=0.001), particularly in the hepatitis B e antigen-positive (P=0.008), tumor recurrence (P=0.002) and <3 cm tumor size (P=0.003) groups. Furthermore, in patients with preoperative cirrhosis, levels of cccDNA and MSL2 mRNA were significantly higher in tumor tissues compared with that in peri-tumor tissues (P<0.001 and P=0.023, respectively). The expression levels of HBx mRNA in antiviral-treated tumors and peri-tumor tissues were significantly lower compared with those in untreated tissues (P=0.026 and P=0.035). The levels of cccDNA and MSL2 mRNA in the HBx-positive group were significantly higher in tumor tissues compared with those in peri-tumor tissues (P=0.026 and P=0.013). In conclusion, cccDNA participated in the tumorigenesis of HBV-associated HCC, and antiviral therapy was found to modulate hepatocarcinogenesis by decreasing the levels of HBx to inhibit the tumorigenic effect of MSL2 and cccDNA.

Copyright © 2019, Spandidos Publications.
KEYWORDS:

covalently closed circular DNA; hepatitis B; hepatitis B virus-encoded X protein; hepatocellular carcinoma; male specific lethal 2

PMID:
    31612010
PMCID:
    PMC6781749
DOI:
    10.3892/ol.2019.10833

StephenW

Oncol Lett。 2019年11月; 18（5）：4984-4991。 doi：10.3892 / ol.2019.10833。 Epub 2019年9月10日
抗病毒治疗可能会降低HBx，从而影响肝癌发生中的cccDNA和MSL2。
Jin XL1，Hong SK1，Kim H1，Lee SK1，Yi NJ1，Lee KW1，Suh KS1。
作者信息

1个
首尔国立大学医学院外科系，韩国首尔03080。

抽象

慢性乙型肝炎病毒（HBV）是肝细胞癌（HCC）的主要原因。共价封闭的环状DNA（cccDNA）是HBV生命周期的中间产物。 HBV编码的X蛋白（HBx）是一种关键的病毒癌蛋白，可以被男性特异性致死因子2（MSL2）特异性泛素化，从而导致HBx活性上调并促进转录，细胞增殖和肿瘤生长。本研究比较了肿瘤和肿瘤周围组织中cccDNA，MSL2 mRNA和HBx mRNA的水平，并阐明了抗病毒治疗对这些指标的影响。使用定量PCR测定了接受肝脏手术的HBV相关HCC患者的肝内cccDNA，MSL2 mRNA和HBx mRNA水平。本研究共纳入50例患者，在手术前，有31例患者接受了抗病毒治疗。与肿瘤周围组织相比，肿瘤组织中的肝内cccDNA水平显着更高（P = 0.001），尤其是在乙型肝炎e抗原阳性（P = 0.008），肿瘤复发（P = 0.002）和<​​3 cm时肿瘤大小（P = 0.003）组。此外，在术前肝硬化患者中，cccDNA和MSL2 mRNA的表达水平均高于未接受治疗的患者。抗病毒治疗的肿瘤和肿瘤周围组织中HBx mRNA的表达水平明显低于未治疗的组织（分别为P <0.001和P = 0.023） ）。肿瘤组织中HBx阳性组的cccDNA和MSL2 mRNA水平明显高于肿瘤周围组织（P = 0.026和P = 0.013）。总之，cccDNA加入了与HBV相关的HCC的肿瘤发生中，并且发现抗病毒疗法通过降低HBx的水平来抑制MSL2和cccDNA的致癌作用，从而调节肝癌的发生。

版权所有©2019，Spandidos Publications。
关键字：

共价封闭的环状DNA；乙型肝炎；乙肝病毒编码的X蛋白；肝细胞癌；男性致死率2

PMID：
31612010
PMCID：
PMC6781749
DOI：
10.3892 / ol.2019.10833