Cisplatin Enhances Hepatitis B Virus Replication and PGC-1α Expression through Endoplasmic Reticulum Stress

Scientific Reports
Xiaosong LiAilong Huang

Abstract

Chronic hepatitis B infection remains a serious public health issue worldwide. Hepatitis B virus (HBV) reactivation is commonly reported in patients receiving anticancer therapy, immunosuppressive therapy, or organ and tissue transplantation. However, the precise mechanisms underlying chemotherapeutic agent-related HBV reactivation remain unclear. Here, we report that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) plays a central role in cisplatin-induced HBV transcription and replication. First, cisplatin treatment upregulated the expression levels of PGC-1α and hepatocyte nuclear factor 4 alpha (HNF-4α) in both HBV-replicating cells and an HBV-transgenic mouse model. PGC-1α coactivates with HNF-4α, which interacts with a core promoter and enhancer II region of HBV genome, thereby promoting HBV production. In contrast, knockdown of PGC-1α and HNF-4α by RNA interference in hepatoma cells reversed HBV activation in response to cisplatin. Additionally, PGC-1α upregulation depended on cisplatin-mediated endoplasmic reticulum (ER) stress. We further observed that the recruitment of cyclic AMP-responsive element-binding protein plays a crucial role for PGC-1α transcriptional activation in cisplatin-tre...Continue Reading

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Citations

Aug 7, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Murali GanesanNatalia A Osna
Mar 25, 2020·World Journal of Gastroenterology : WJG·Murali GanesanNatalia A Osna
Jan 29, 2019·BioMed Research International·Lixia GuoXiaosong Li
May 14, 2021·Molecular and Cellular Biochemistry·Qichuang LiuShide Lin

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Methods Mentioned

BETA
PCR
transgenic
immunoprecipitation
immunoprecipitation assay
ChIP
ELISA
environmental stress
electrophoresis

Software Mentioned

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Image Pro Plus
Pro Plus

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