Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover

Oncogene
H-C ChiK-H Lin

Abstract

Infection by hepatitis B virus (HBV) accounts for 50-80% of hepatocellular carcinoma (HCC) development worldwide, in which the HBV-encoded X protein (HBx) has critical role in the induction of carcinogenesis. Several studies have shown that thyroid hormone (TH) suppresses HCC development and protects hepatocytes from HBx-induced damage, thus it is of interest to examine whether TH can protect hepatocytes from HBx-induced carcinogenesis. By treating HBx- transgenic mice with or without TH, we confirmed the protective effects of TH on HBx-induced hepatocarcinogenesis, which was achieved via reduction of reactive oxygen species (ROS) inflicted DNA damage. We further found that TH induced biogenesis of mitochondria (MITO) and autophagy of HBx-targeted MITO simultaneously, consequently leading to suppression of HBx-promoted ROS and carcinogenesis. Using microarray data analysis, this protective effect of TH was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomit...Continue Reading

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Citations

Aug 23, 2017·International Journal of Molecular Sciences·Panagiotis V S VasileiouConstantinos Pantos
Jan 23, 2019·Endocrine-related Cancer·Weijun WeiQuan-Yong Luo
Nov 8, 2018·Endocrine-related Cancer·Yang-Hsiang LinKwang-Huei Lin
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Oct 21, 2020·Biomedical Journal·Po-Shuan HuangKwang-Huei Lin
Oct 9, 2021·Current Pharmaceutical Design·Li-Ping YuXing-Xin Yang

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