Data from HBx-Induced HSPA8 Stimulates HBV Replication and Suppresses Ferroptosis to Support Liver Cancer Progression

• DOI: 10.1158/0008-5472.c.6514397.v2
• Publication Date: 2023-04-05T02:10:45Z
• Authors: Yufei Wang; Man Zhao; Lina Zhao; Yu Geng; Guanghao Li; Lin Chen; Jingxuan Yu; Hongfeng Yuan; Huihui Zhang; Haolin Yun; Ying Yuan; Guowen Wang; Jinyan Feng; Liang Xu; Shuai Wang; Chunyu Hou; Guang Yang; Ningning Zhang; Wei Lu; Xiaodong Zhang
• Keywords: HBx; cccDNA; HSF1; Liver Cancer

<div>Abstract<p>Hepatitis B virus (HBV) infection is a major driver of hepatocarcinogenesis. Ferroptosis type iron-mediated cell death that can suppress liver transformation. Previous studies have linked HBV to ferroptosis in fibrosis and acute failure. However, whether involved HBV-mediated cancer poorly understood. Here, we identified heat shock protein family A member 8 (HSPA8) as crucial host factor modulates replication cancer. Hepatitis X (HBx) upregulated HSPA8 by coactivating the transcription 1 (HSF1) cells. enhanced recruiting hepatitis core (HBc) covalently closed circular DNA (cccDNA) minichromosome, forming positive feedback loop. Moreover, suppressed cells upregulating expression SLC7A11/GPX4 decreasing erastin-mediated reactive oxygen species Fe<sup>2+</sup> accumulation <i>in vitro</i> vivo</i>. Inhibition reduced growth HBV-positive tumors increased sensitivity erastin. In conclusion, HBx-elevated regulates both Targeting could be promising strategy for controlling hepatocarcinogenesis.</p>Significance:<p>HBV-induced upregulation promotes hepatocarcinogenesis suppressing stimulating replication, identifying potential therapeutic target cancer.</p></div>