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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Sci Rep. 2018 Feb 22 ;8(1):3496. Epub 2018 Feb 22. PMID: 29472690

Abstract Author(s):

Xiaosong Li, E Pan, Junke Zhu, Lei Xu, Xuemei Chen, Jingjing Li, Li Liang, Yuan Hu, Jie Xia, Juan Chen, Wannan Chen, Jieli Hu, Kai Wang, Ni Tang, Ailong Huang

Article Affiliation:

Xiaosong Li

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-treated cells. Finally, pharmacologic inhibition of ER stress impaired PGC-1α upregulation and HBV production induced by cisplatin treatment. These findings demonstrate novel molecular mechanisms indicating that ER stress-PGC1α signaling pathway plays a critical role in cisplatin-evoked HBV reactivation.

Study Type : Transgenic Animal Study

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Sayer Ji
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