Hepatitis B Virus X gene in Hepatocellular Carcinoma
A Viral Biorealm page on the family Hepatitis B Virus X gene in Hepatocellular Carcinoma
miRNAs are short, endogenous RNA molecules of 19- to 24- nucleotides in length that are expressed widely in eukaryotes that [1]. The main function of a miRNA is to bind its complementary (target) mRNA sequence and inhibit translation, a process known as RNA silencing. Since plants, fungi, and animals have evolved RNA silencing as an innate antiviral mechanism, it is not surprising that an infecting virus can induce changes in cellular miRNA or synthesize viral miRNA the antiviral activities of its host [2]. A common goal of many hepatitis B virus (HBV) researchers is to identify the roles of host miRNAs in replication an pathogenesis of the virus. Furthermore, particular interactions between host miRNAs and HBV have been correlated with instance and _____ of hepatocellular carcinoma.
First subtopic
hep b infection, HCC
Hepatitis B Virus Protein x in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is among the most frequently diagnosed cancers worldwide. For over forty years physicians and researchers have observed an association between HBV infection and development of HCC. Of the seven HBV genes, hepatitis b virus x protein (HBx, 17.5 kDa) is the smallest and required extensive efforts to characterize; its elusiveness is highlighted by its designation “X.” The protein functions as a transcriptional transactivator of both viral and cellular transcripts, in addition inducing cytoplasmic signal transduction pathways [enigmatic]. Interestingly, HBx was a more potent inducer of transcription upon deletion of its N-terminal 1 to 50-amino-acid fragment, suggesting this domain may function as a negative regulatory element [enigmatic]. In vitro, HBx binds eukaryotic basal transcription factors essential for proper RNAP II-DNA interactions and promoter escape, including TATA-binding protein (TBP), TFIIB, TFIIH, and the RNAP subunit RPB5 [TATA paper, enigmatic]. HBx has been shown to suppress apoptosis of hepatocytes via induction of survivin, disruption of the tumor suppressor p53, and activation of c-jun N-terminal kinases [ .., …, activated ras oncogene]. In infected cells, HBx induces overexpression of a cellular target, HBXIP, which functions as a regulator of centrosome dynamics and cytokinesis – critical aspects of mitosis. Furthermore, it was reported that HBx activates src and the ras/raf/ERK (extracellular signal-regulated kinase) pathway, which leads to proliferation of quiescent cells [activated ras oncogene]. These findings suggest that HBx is a key mediator of HCC development in HBV infected individuals. Since the first report of a miRNA possessing antiviral properties in 2005 [A cellular microRNA mediates antiviral defense in human cells], researchers have begun to explore the possibility of interactions between host miRNAs and HBV. These interactions may provide key mechanistic insights regarding the role of HBx in host gene expression and development and HCC in HBV-infected individuals. HBV enhancers… open reading frames… in other section… mention how HBV relies on host transcription factors…
Overview of Interactions between HBV and Host miRNAs
Several cellular transcription factors have an affinity for HBV enhancer elements and thus are crucial for efficient viral replication. A 2011 review reported C/EBP and CREB as TFs necessary for efficient viral replication. C/EBP is “CAAT enhancer-binding protein,” designated as such because of its affinity for the CAAT promoter motif, and CREB is cAMP-response element binding protein. Since publication of the review, Hu et al reported peroxisome proliferator-activated receptor alpha (PPARA) as another TF that binds viral enhancer elements and induces transcription of viral genes. Many of these TFs are identified in silico by screening for host miRNAs with HBV mRNA sequence alignment. The miRNA that targets PPARA (miRNA-141) was selected in a preliminary screening of “hit” sequences because it was the most effective miRNA in inhibiting the rate of HBV replication in a screen of 64 miRNA sequences…
References
Beck, Juergen, and Michael Nassal. "World Journal of Gastroenterology." 13.1 (2007): 48-64.
Bouchard, MJ, and RJ Schneider. "Journal of Virology." 78.23 (2004): 12725-12734.
Marusawa, H, S Matsuzawa, et al. "The EMBO Journal."EMBO Journal. 22.11 (2003): 2729-2740.
Cheng, Alfred A.L., Jun Yu, et al. "Biochemical and Biophysical Research Communications."(2008)
Qadri, I, H Maguire, et al. "Proceedings of the National Academy of Sciences." 92. (1995): 1003-1007.
Liu, Wan-Hsin, Shiou-Hwei Yeh, et al. "Biochemica et Biophysica Acta." Biochemica et Biophysica Acta. (2011): 678-685.
Ren, Min, Dongdong Qin, et al. "Antiviral Research." 94. (2012): 225-231.
He, Yan, Hui-qing Sun, et al. "Medical Oncology." 27. (2009): 1227-1233.
