Profiling of LINE-1-Related Genes in Hepatocellular Carcinoma

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.

Characterization of an active LINE-1 in the naked mole-rat genome

“…In addition, we reasoned that such secrets likely include low retrotransposition activity since the NMR genome contains fewer retrotransposons than other mammalian genomes 7 . L1 is a retrotransposon that is considered to be an endogenous mutagen, which can cause oncogenic mutations and contribute to cancer development 9 – 13 . In this study, we, for the first time, cloned an intact L1 from the NMR genome and determined its retrotransposition activity.…”

“…Another feature of NMRs that may be related to cancer resistance is fewer transposon-derived sequences than found in other mammals (25% in the NMR, 41% in the human, 38% in the mouse and 36% in the rat genomes) 7 . Transposons, such as endogenous retroviruses (ERVs) and long interspersed elements (LINEs), can autonomously amplify themselves in the genome 8 , which may produce oncogenic mutations and/or induce genomic instability, thereby promoting cancer development 9 – 13 . Thus, fewer transposon-derived sequences may indicate lower transposition activity of the NMR transposons, which may contribute to NMR cancer resistance.…”

“…L1 retrotransposition occurs by target-site primed reverse transcription (TPRT), during which ORF2p makes a nick in genomic DNA and synthesizes L1 cDNA using the 3′ hydroxyl group at the nick 16 . The active retrotransposition of L1 is considered a major source of endogenous mutagenesis that can promote cancer development 9 – 13 . Consistently, we have found that Kaposi’s sarcoma-associated herpesvirus, an oncogenic virus, stimulates L1 retrotransposition, thereby enhancing transformation 17 .…”

Bornavirus infection in human diseases and its molecular neuropathology

“…As L1 retrotransposition is strictly limited, because dysregulation of L1 activity is harmful for the host in most cases, BoDV‐1 infection might disturb the L1 retrotransposition required for generating neuronal variations and thereby impair brain function (Figure 3A). 104–106 Bornavirus integrants have been shown to affect the expression of neighboring genes, suggesting another possibility that BoDV‐1 infection might alter host gene expression through the integration of viral cDNA, thereby impairing brain function (Figure 3B). 107,108 Collectively, these ideas suggest that alterations in neurogenesis occur during BoDV‐1 infection, which can reduce synaptic plasticity and impair brain function.…”

A Traditional Chinese Medicine, Maoto, Suppresses Hepatitis B Virus Production

“…Hepatitis B is an infectious disease caused by hepatitis B virus (HBV). Despite the development of an effective vaccine, more than 250 million HBV carriers still exist, and 887,000 deaths occurred in 2015 due to acute and chronic HBV-related diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (Dienstag, 2008;Schweitzer et al, 2015;WHO, 2015;Honda and Rahman, 2019). Disease progression and severity mostly depend on multiple viral and host factors (Rahman et al, 2016;Al-Sadeq et al, 2019;Jia et al, 2019;Hossain et al, 2020).…”