Abstract
Hepatocellular carcinoma (HCC) is a prime public health concern that accounts for most of the primary liver malignancies in humans. The most common etiological factor of HCC is hepatitis B virus (HBV). Despite recent advances in treatment strategies, there has been little success in improving the survival of HCC patients. To develop a novel therapeutic approach, evaluation of a working hypothesis based on different viewpoints might be important. Long interspersed element 1 (L1) retrotransposons have been suggested to play a role in HCC. However, the molecular machineries that can modulate L1 biology in HBV-related HCC have not been well-evaluated. Here, we summarize the profiles of expression and/or activation status of L1-related genes in HBV-related HCC, and HBV- and HCC-related genes that may impact L1-mediated tumorigenesis. L1 restriction factors appear to be suppressed by HBV infection. Since some of the L1 restriction factors also limit HBV, these factors may be exhausted in HBV-infected cells, which causes de-suppression of L1. Several HBV- and HCC-related genes that interact with L1 can affect oncogenic processes. Thus, L1 may be a novel prime therapeutic target for HBV-related HCC. Studies in this area will provide insights into HCC and other types of cancers.
Highlights
Hepatocellular carcinoma (HCC) is a prime public health concern that causes almost 90% of the primary liver malignancies in humans
Over 50% of hepatitis B virus (HBV) patients with chronic HBV infections progress to liver cirrhosis (LC) and 70% to 90% of them eventually develop HCC [5,6]
During HBV infection, the HBV partially double-stranded DNA genome is repaired and converted into covalently closed circular DNA that can act as a template for the synthesis of viral transcripts including pre-genomic RNA [8,9,10,11]. pgRNA is reverse-transcribed to generate rcDNA for viral replication [10]
Summary
Hepatocellular carcinoma (HCC) is a prime public health concern that causes almost 90% of the primary liver malignancies in humans. There is an increased risk of developing HCC in adult males and chronic hepatitis B patients with cirrhosis who contracted HBV in early childhood [3]. During TPRT, L1 creates a nicked DNA strand, which serves as a primer for reverse transcription, using the endonuclease activity of ORF2p Environmental factors, such as chemicals, oxidative stress and infection, are capable of affecting L1 retrotransposition [32,41,42,43]. In the HBV life cycle, SAMHD1 has no effect on covalently closed circular DNA (cccDNA) production or HBV gene expression, while it inhibits the reverse-transcription step through the depletion of cellular dNTPs (Figure 1A) [70]. HBV may suppress the MOV10 expression, thereby enhancing L1 retrotransposition in infected hepatocytes (Figure 1A)
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