2. Academic Validation
  3. HBx-induced HSPA8 stimulates HBV replication and suppresses ferroptosis to support liver cancer progression

HBx-induced HSPA8 stimulates HBV replication and suppresses ferroptosis to support liver cancer progression

  • Cancer Res. 2023 Feb 6;CAN-22-3169. doi: 10.1158/0008-5472.CAN-22-3169.
Yufei Wang 1,  Man Zhao 2,  Lina Zhao 1,  Yu Geng 3,  Guanghao Li 4,  Lin Chen 5,  Jingxuan Yu 3,  Hongfeng Yuan 2,  Huihui Zhang 1,  Haolin Yun 2,  Ying Yuan 2,  Guowen Wang 4,  Jinyan Feng 6,  Liang Xu 7,  Shuai Wang 4,  Chunyu Hou 8,  Guang Yang 1,  Ning-Ning Zhang 1,  Wei Lu 1,  Xiaodong Zhang 1
Affiliations

Affiliations

  • 1 Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
  • 2 Nankai University, Tianjin, China.
  • 3 Nankai University, China.
  • 4 Tianjin Medical University Cancer Institute and Hospital, China.
  • 5 Tianjin Second People's Hospital, China.
  • 6 Tianjin Medical University Cancer Institute and Hospital, tianjin, China.
  • 7 Tianjin Second People's Hospital, Tianjin, China.
  • 8 Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin, China.
PMID: 36745032 DOI: 10.1158/0008-5472.CAN-22-3169
Abstract

Hepatitis B virus (HBV) Infection is a major driver of hepatocarcinogenesis. Ferroptosis is a type of iron-mediated cell death that can suppress liver transformation. Previous studies have linked HBV to Ferroptosis in liver fibrosis and acute liver failure. However, whether Ferroptosis is involved in HBV-mediated liver Cancer is poorly understood. Here, we identified heat shock protein family A member 8 (HSPA8) as a crucial host factor that modulates HBV replication and Ferroptosis in liver Cancer. Hepatitis B X protein (HBx) upregulated HSPA8 by coactivating the transcription factor heat shock factor 1 (HSF1) in cells. HSPA8 enhanced HBV replication by recruiting hepatitis B core protein (HBc) to the HBV covalently closed circular DNA (cccDNA) minichromosome, forming a positive feedback loop. Moreover, HSPA8 suppressed Ferroptosis in liver Cancer cells by upregulating expression of SLC7A11/GPX4 and decreasing erastin-mediated ROS and Fe2+ accumulation in cells in vitro and in vivo. Inhibition of HSPA8 reduced the growth of HBV-positive liver tumors and increased sensitivity to erastin. In conclusion, HBx-elevated HSPA8 regulates both HBV replication and Ferroptosis in liver Cancer. Targeting HSPA8 could be a promising strategy for controlling HBV and hepatocarcinogenesis.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z