Zuo Kai, Kong Li, Xue Dong, Yang Yanyan, Xie Linlin
Department of Infectious Diseases, Binzhou People's Hospital, No. 515, The Seventh Yellow River Road, Binzhou, 256610, Shandong, China.
Department of Pharmacy Intravenous Admixture Services, Binzhou People's Hospital, Binzhou, Shandong, China.
Virus Genes. 2018 Aug;54(4):475-483. doi: 10.1007/s11262-018-1564-1. Epub 2018 May 22.
Chronic infection with hepatitis B virus (HBV) is one of most important risk factors for the development of hepatocellular carcinoma (HCC). Several long non-coding RNAs (lncRNAs) have been shown to be involved in the etiology of HBV-related HCC. AX800134 is one recently identified lncRNA associated with HCC. In this study, we validated the upregulated expression of AX800134 in HBV-positive HCC compared with HBV-negative HCC. Furthermore, we found that HBV X protein (HBx) directly triggered AX800134 expression in human hepatoma HepG2 cells. Pro-inflammatory cytokine TNFα also induced AX800134 upregulation in HBx-expressing HepG2 cells, which could be reversed by reactive oxygen species (ROS) scavenger pyrrolidine dithiocarbamate (PDTC). Additionally, silencing AX800134 with siRNA interference remarkably inhibited the growth and invasion of HBx-expressing HepG2 cells. AX800134 antagonism also enhanced spontaneous apoptosis of HepG2 cells under serum deprivation condition. Therefore, our results indicate that highly expressed AX800134 acts as an oncogenic factor in HCC, and its upregulation is related with the viral product HBx and chronic inflammation.
慢性乙型肝炎病毒(HBV)感染是肝细胞癌(HCC)发生的最重要危险因素之一。已有研究表明,几种长链非编码RNA(lncRNA)参与了HBV相关HCC的发病机制。AX800134是最近发现的一种与HCC相关的lncRNA。在本研究中,我们验证了与HBV阴性HCC相比,AX800134在HBV阳性HCC中表达上调。此外,我们发现HBV X蛋白(HBx)可直接在人肝癌HepG2细胞中触发AX800134的表达。促炎细胞因子TNFα也可在表达HBx的HepG2细胞中诱导AX800134上调,而活性氧(ROS)清除剂吡咯烷二硫代氨基甲酸盐(PDTC)可逆转这种上调。此外,用siRNA干扰沉默AX800134可显著抑制表达HBx的HepG2细胞的生长和侵袭。AX800134拮抗作用还可增强血清剥夺条件下HepG2细胞的自发凋亡。因此,我们的结果表明,高表达的AX800134在HCC中起致癌作用,其上调与病毒产物HBx和慢性炎症有关。