CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice

Liu, Yongzhen; Qi, Xuewei; Zeng, Zhenzhen; Wang, Lu; Wang, Jie; Zhang, Ting; Xu, Qiang; Shen, Congle; Zhou, Guangde; Yang, Shaomin; Chen, Xiangmei; Lu, Fengmin

doi:10.1038/s41598-017-03070-8

Cited by 47 publications

(40 citation statements)

References 44 publications

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“…Tward et al reported that about three quarters of mice developed HCC in 1 month after HGD injection of transposon carrying Met and β-catenin gene (Tward et al, 2007 ). Besides, the researchers also tried CRISPR/Cas9-mediated gene editing, which allowed rapid occurrence of liver tumors, by regulating oncogenes or tumor suppressor genes expression in somatic cells (Liu et al, 2017 ).…”

Section: Establishment Of Hepatocellular Carcinoma Models By Hgdmentioning

confidence: 99%

Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

et al. 2017

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Development of an safe and efficient in vivo gene delivery method is indispensable for molecular biology research and the progress in the following gene therapy. Over the past few years, hydrodynamic gene delivery (HGD) with naked DNA has drawn increasing interest in both research and potential clinic applications due to its high efficiency and low risk in triggering immune responses and carcinogenesis in comparison to viral vectors. This method, involving intravenous injection (i.v.) of massive DNA in a short duration, gives a transient but high in vivo gene expression especially in the liver of small animals. In addition to DNA, it has also been shown to deliver other substance such as RNA, proteins, synthetic small compounds and even viruses in vivo. Given its ability to robustly mimic in vivo hepatitis B virus (HBV) production in liver, HGD has become a fundamental and important technology on HBV studies in our group and many other groups. Recently, there have been interesting reports about the applications and further improvement of this technology in other liver research. Here, we review the principle, safety, current application and development of hydrodynamic delivery in liver disease studies, and discuss its future prospects, clinical potential and challenges.

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Section: Establishment Of Hepatocellular Carcinoma Models By Hgdmentioning

confidence: 99%

Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

et al. 2017

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“…92 To better address its underlying aetiology, Liu et al used HBV transgenic mice in combination with CRISPR/Cas9 mediated deletion of p53 and Pten. 93 Although the authors deleted the same 2 tumour suppressor genes as in a previous study, 47 their tumours presented as HCC not ICC and were cytokeratin 19-negative. The reason for this discrepancy is unclear despite the distinct settings, namely carbon tetrachloride or transgenic HBV.…”

Section: Intrahepatic Cholangiocarcinomamentioning

confidence: 84%

Using CRISPR/Cas9 to model human liver disease

et al. 2019

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CRISPR/Cas9 gene editing has revolutionised biomedical research. The ease of design has allowed many groups to apply this technology for disease modelling in animals. While the mouse remains the most commonly used organism for embryonic editing, CRISPR is now increasingly performed with high efficiency in other species. The liver is also amenable to somatic genome editing, and some delivery methods already allow for efficient editing in the whole liver. In this review, we describe CRISPR-edited animals developed for modelling a broad range of human liver disorders, such as acquired and inherited hepatic metabolic diseases and liver cancers. CRISPR has greatly expanded the repertoire of animal models available for the study of human liver disease, advancing our understanding of their pathophysiology and providing new opportunities to develop novel therapeutic approaches.

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“…Importantly, several of these miRNAs target the main inhibitor of the PI3K/AKT pathway, PTEN protein, and its mutations were found in HCC patients [ 42 ]. In accordance, PTEN deficient mice have been shown to develop steatosis, hepatomegaly, and HCCs [ 43 , 44 ].…”

Section: Molecular Mechanisms Involved In Nash-related Hccmentioning

confidence: 95%

Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma

Kutlu

Kaleli

Özer

2018

Canadian Journal of Gastroenterology and Hepatology

119

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The proportion of obese or diabetic population has been anticipated to increase in the upcoming decades, which rises the prevalence of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). Recent evidence indicates that NASH is the main cause of chronic liver diseases and it is an important risk factor for development of hepatocellular carcinoma (HCC). Although the literature addressing NASH-HCC is growing rapidly, limited data is available about the etiology of NASH-related HCC. Experimental studies on the molecular mechanism of HCC development in NASH reveal that the carcinogenesis is relevant to complex changes in signaling pathways that mediate cell proliferation and energy metabolism. Genetic or epigenetic modifications and alterations in metabolic, immunologic, and endocrine pathways have been shown to be closely related to inflammation, liver injury, and fibrosis in NASH along with its subsequent progression to HCC. In this review, we provide an overview on the current knowledge of NASH-related HCC development and emphasize molecular signaling pathways regarding their mechanism of action in NASH-derived HCC.

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CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice

Cited by 47 publications

References 44 publications

Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

Using CRISPR/Cas9 to model human liver disease

Molecular Pathogenesis of Nonalcoholic Steatohepatitis- (NASH-) Related Hepatocellular Carcinoma

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