Roles of APOBEC3 in hepatitis B virus (HBV) infection and hepatocarcinogenesis

Figures & data

Figure 1. The process of HBV infecting liver cells and mechanisms of A3 genes in anti-HBV

Table 1. Studies investigated A3 genes and HCC development

Author	Year	A3 genes	Cell lines	Participants	Main findings	Reference
He X, et al	2019	A3A, A3B, A3H	/	HBV-related HCC: 285; CHB: 104; HBV-related cirrhosis: 265	No relationship showed between A3A, A3B and A3H SNPs and CHB progression or HCC development.	[26]
Yang Z, et al	2015	A3A, A3B, A3C, A3D, A3F, A3G, A3H	/	HCC: 240	A3G and A3F were risk factors for HCC progression and survival; A3C and A3H might play favorable roles in HCC aggressineness and survival.	[32]
Yang Z, et al	2015	A3A, A3B, A3C, A3F, A3G	/	HBV-related HCC: 220	A3F was a risk facor for HBV-related HCC recurrence.	[33]
Luo X, et al	2016	A3A, A3B, A3C, A3D, A3F, A3G, A3H	/	HCC: 49	A3B contributed to cccDNA editing and subsequent degradation in cancerous tissues.	[44]
Xu R, et al	2007	A3A, A3B, A3C, A3G, A3F	HepG2	HCC: 29	A3B promoted the growth of neoplastic human HepG2 liver cells and up-regulated heat shock transcription factor1 (HSF1) expression; Some A3 genes (A3B, A3C, A3F and A3G) play a role in the carcinogenesis of HCC through the generation of HBx mutants.	[45]
Yang Z, et al	2018	A3F	SK-Hep1; Bel-7404	HCC: 8	A3F was upregulated in tumor samples and promoted cell proliferation and migration.	[46]
Liu W, et al	2019	A3B	/	Health controls: 1449; HBV clearence subjects: 300; ASC: 511; CHB: 1016; HBV-related cirrhosis: 674; HBV-related HCC: 1271	A3B rs2267401-G and UNG rs3890995-C allele were significantly increased HCC risk. A3B rs2267401-GG genotype, higher A3B, and higher A3B/UNG expression ratio predicted poor HCC prognosis.	[93]

ASC, asymptomatic hepatitis B virus carriers; CHB, chronic hepatitis B; HCC, hepatocellular carcinoma; SNPs, single nucleotide polymorphisms.

He X, Xu H, Wang X, et al. Gao P: associations between the single nucleotide polymorphisms of APOBEC3A, APOBEC3B and APOBEC3H, and chronic hepatitis B progression and hepatocellular carcinoma in a Chinese population. Mol Med Rep. 2019;20(3):2177–2188.

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Yang Z, Lu Y, Xu Q, et al. Chen X: correlation of APOBEC3 in tumor tissues with clinico-pathological features and survival from hepatocellular carcinoma after curative hepatectomy. Int J Clin Exp Med. 2015;8(5):7762–7769.

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Yang Z, Zhuang L, Yu Y, et al. Chen X: overexpression of APOBEC3F in tumor tissues is potentially predictive for poor recurrence-free survival from HBV-related hepatocellular carcinoma. Discov Med. 2015;20(112):349–356.

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Luo X, Huang Y, Chen Y, et al. Hu Y: association of Hepatitis B Virus covalently closed circular DNA and human APOBEC3B in Hepatitis B Virus-related hepatocellular carcinoma. PLoS One. 2016;11(6):e0157708.

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Xu R, Zhang X, Zhang W, et al. Yu XF: association of human APOBEC3 cytidine deaminases with the generation of hepatitis virus B x antigen mutants and hepatocellular carcinoma. Hepatology. 2007;46(6):1810–1820.

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Yang Z, Tao Y, Xu X, et al. Ma L: bufalin inhibits cell proliferation and migration of hepatocellular carcinoma cells via APOBEC3F induced intestinal immune network for IgA production signaling pathway. Biochem Biophys Res Commun. 2018;503(3):2124–2131.

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Liu W, Wu J, Yang F, et al. Genetic polymorphisms predisposing the interleukin 6-induced APOBEC3B-UNG imbalance increase HCC risk via promoting the generation of APOBEC-Signature HBV mutations. Clin Cancer Res. 2019;25(18):5525–5536.

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Data Availability Statement:

Not applicable.