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Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression.

ABSTRACT: Hepatitis B virus (HBV) X protein (HBx) is associated with hepatocarcinogenesis. E2-EPF ubiquitin carrier protein (UCP) catalyzes ubiquitination of itself and von Hippel-Lindau protein (pVHL) for degradation and associates with tumor growth and metastasis. However, it remains unknown whether HBx modulates the enzyme activity of UCP and thereby influences hepatocarcinogenesis. Here, we show that UCP is highly expressed in liver tissues of HBx-transgenic mice, but not non-transgenic mice. UCP was more frequently expressed in HBV-positive liver cancers than in HBV-negative liver cancers. HBx binds to UCP specifically and serotype independently, and forms a ternary complex with UCP and pVHL. HBx inhibits self-ubiquitination of UCP, but enhances UCP-mediated pVHL ubiquitination, resulting in stabilization of hypoxia-inducible factor-1α and -2α. HBx and UCP stabilize each other by mutually inhibiting their ubiquitination. HBx promotes cellular proliferation and metastasis via UCP. Our findings suggest that UCP plays a key role in HBV-related hepatocarcinogenesis.

SUBMITTER: Lim JH

PROVIDER: S-EPMC6586911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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E2-EPF UCP Possesses E3 Ubiquitin Ligase Activity via Its Cysteine 118 Residue.

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Hepatocellular carcinoma progression mediated by hepatitis B virus-encoded circRNA HBV_circ_1 through interaction with CDK1.

Project description:Hepatitis B virus (HBV) produces circular RNA (circRNA), whose functions have not yet been clearly elucidated. In this study, a novel circRNA HBV_circ_1 produced by HBV was identified in HBV-positive HepG2.2.15 cells and HBV-related hepatocellular carcinoma (HCC) tissue (HCCT). Microarray analysis of 68 HCCT samples showed that HBV_circ_1 abundance was significantly higher than that in paracancerous tissues. In addition, survival rate of HBV_circ_1-positive patients was significantly lower compared with HBV_circ_1-negative patients. Transient expression indicated that HBV_circ_1 enhanced cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Furthermore, ectopical HBV_circ_1 expression increased tumor size in vivo. HBV_circ_1 was confirmed to interact with cyclin-dependent kinase 1 (CDK1) to regulate cell proliferation. These results suggest that HCC progression may be promoted by interaction of HBV_circ_1 with CDK1. Our data not only showed a novel clue to understand carcinogenesis and progress of HBV-related HCC but also provided a new target for the development of therapeutic drugs.

| S-EPMC8463320 | biostudies-literature

Molecular Signature of Hepatitis D Virus-Associated Hepatocellular Carcinoma

Project description:To investigate the role of viral and host factors in HDV-associated HCC we carried out an integrated clinicopathological and gene expression study of tissue specimens and laser microdissected hepatocytes obtained at the time of liver transplantation from livers with HDV-HCC, HDV-cirrhosis without HCC, HCV-HCC and HBV-HCC. References to GSM series of HDV and HBV livers, already deposited in GEO, are included in this series. Part of data of HCV livers are a re-analysis of GSE series GSE69715 and GSE78737, the re-analyzed GSM is indicated in the 'description' column and with a link at the bottom of the page.

2018-04-09 | GSE107170 | GEO

Molecular Signature of Hepatitis D Virus-Associated Hepatocellular Carcinoma

Project description:To investigate the role of viral and host factors in HDV-related HCC we analyzed the serum, tissue specimens and laser microdissected hepatocytes obtained at the time of liver transplantation from five patients with HDV-HCC. Livers of seven patients with HDV-cirrhosis without HCC were also analyzed. We carried out an integrated clinicopathological analysis and gene expression profiling,

2018-04-09 | GSE98383 | GEO

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Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression.

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| S-EPMC8752572 | biostudies-literature

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