To Jeffrey C, Chiu Amy P, Tschida Barbara R, Lo Lilian H, Chiu Cynthia H, Li Xiao-Xiao, Kuka Timothy P, Linden Michael A, Amin Khalid, Chan Wing-Cheung, Bell Jason B, Moriarity Branden S, Largaespada David A, Keng Vincent W
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR.
Masonic Cancer Center, Department of Pediatrics, and Center for Genome Engineering, University of Minnesota, Minneapolis, MN, 55455, USA.
JHEP Rep. 2020 Dec 19;3(2):100223. doi: 10.1016/j.jhepr.2020.100223. eCollection 2021 Apr.
BACKGROUND & AIMS: Zinc finger and BTB domain containing 20 () has been implicated as a potential oncogene in liver cancer. However, knockout studies have shown it to be a transcriptional repressor of the alpha-foetoprotein () gene in adult liver, and reduced levels of allow for upregulation of with increased tumour severity in certain cases of hepatocellular carcinoma (HCC). As there are many discrepancies in the literature regarding its role in liver tumourigenesis, the aim of this study was to elucidate the role of in HCC tumourigenesis.
A reverse genetic study using the Sleeping Beauty () transposon system in mice was performed to elucidate the role of in HCC tumourigenesis. gain- and loss-of-function experiments were used to assess the relationship amongst ZBTB20, peroxisome proliferator activated receptor gamma (PPARG) and catenin beta 1 (CTNNB1).
Transgenic overexpression of in hepatocytes and in the context of transformation related protein ( ) inactivation induced hepatic hypertrophy, activation of WNT/CTNNB1 signalling, and development of liver tumours. overexpression and knockout experiments using CRISPR/Cas9 demonstrated the important role for ZBTB20 in downregulating PPARG, resulting in activation of the WNT/CTNNB1 signalling pathway and its downstream effectors in HCC tumourigenesis.
These findings demonstrate a novel interaction between ZBTB20 and PPARG, which leads to activation of the WNT/CTNNB1 signalling pathway in HCC tumourigenesis.
has been implicated as a potential oncogene in liver cancer. Herein, we uncover its important role in liver cancer development. We show that it interacts with PPARG to upregulate the WNT/CTNNB1 signalling pathway, leading to tumourigenesis.
含锌指和BTB结构域的20（ZBTB20）被认为是肝癌中的一种潜在致癌基因。然而，基因敲除研究表明它是成年肝脏中甲胎蛋白（AFP）基因的转录抑制因子，在某些肝细胞癌（HCC）病例中，ZBTB20水平降低会随着肿瘤严重程度增加而导致AFP上调。由于文献中关于其在肝脏肿瘤发生中的作用存在许多差异，本研究的目的是阐明ZBTB20在HCC肿瘤发生中的作用。
利用小鼠中的睡美人（SB）转座子系统进行反向遗传学研究，以阐明ZBTB20在HCC肿瘤发生中的作用。采用ZBTB20功能获得和缺失实验来评估ZBTB20、过氧化物酶体增殖物激活受体γ（PPARG）和连环蛋白β1（CTNNB1）之间的关系。
在肝细胞中以及在转化相关蛋白（TRβ）失活的背景下，ZBTB20的转基因过表达诱导了肝脏肥大、WNT/CTNNB1信号通路激活以及肝肿瘤的发生。使用CRISPR/Cas9进行的ZBTB20过表达和基因敲除实验证明了ZBTB20在下调PPARG方面的重要作用，从而导致HCC肿瘤发生中WNT/CTNNB1信号通路及其下游效应物的激活。
这些发现证明了ZBTB20与PPARG之间的新型相互作用，这导致了HCC肿瘤发生中WNT/CTNNB1信号通路的激活。
ZBTB20被认为是肝癌中的一种潜在致癌基因。在此，我们揭示了它在肝癌发展中的重要作用。我们表明它与PPARG相互作用以上调WNT/CTNNB1信号通路，从而导致肿瘤发生。
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