In:
Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-2-10)
Abstract:
We aimed to elucidate the mechanism by which hepatitis B virus X (HBx) mutations increase the occurrence of hepatocellular carcinoma (HCC) and identify novel putative therapeutic targets. Wild-type HBx (WT-HBx) and four HBx mutants (M1, A1762T/G1764A; M2, T1674G+T1753C+A1762T/G1764A; M3, C1653T+T1674G+A1762T/G1764A; and Ct-HBx, carboxylic acid-terminal truncated HBx) were delivered into Sleeping Beauty ( SB ) mouse models. The HCC incidence was higher in the M3-HBx- and Ct-HBx-injected SB mice. M3-HBx had a stronger capacity of upregulating inflammatory cytokines than other HBx variants. Ectopic expression of M3-HBx and Ct-HBx significantly increased proliferation and S phase proportion of HepG2 and HeLa cells, compared to WT-HBx. Plasminogen activator inhibitor-1 (PAI1) and cell division cycle 20 (CDC20) were identified as novel effectors by cDNA microarray analysis. M3-HBx and Ct-HBx significantly upregulated the expression of PAI1 and CDC20 in HepG2 and HeLa cells as well as the livers of SB mice. Silencing PAI1 attenuated the effects of M3-HBx and Ct-HBx on the growth of HepG2 and HeLa cells. PAI1, an important player bridging the HBx mutants and HCC, should be a promising candidate as a prognostic biomarker and therapeutic target in HBV-related HCC.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2022.836517
DOI:
10.3389/fonc.2022.836517.s001
DOI:
10.3389/fonc.2022.836517.s002
DOI:
10.3389/fonc.2022.836517.s003
DOI:
10.3389/fonc.2022.836517.s004
DOI:
10.3389/fonc.2022.836517.s005
DOI:
10.3389/fonc.2022.836517.s006
DOI:
10.3389/fonc.2022.836517.s007
DOI:
10.3389/fonc.2022.836517.s008
DOI:
10.3389/fonc.2022.836517.s009
DOI:
10.3389/fonc.2022.836517.s010
DOI:
10.3389/fonc.2022.836517.s011
DOI:
10.3389/fonc.2022.836517.s012
DOI:
10.3389/fonc.2022.836517.s013
DOI:
10.3389/fonc.2022.836517.s014
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2649216-7
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