ArticleJournal of cancer research and clinical oncology2020
Genome-wide CRISPR knockout screens identify ADAMTSL3 and PTEN genes as suppressors of HCC proliferation and metastasis, respectively.
Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 43 citations in OpenAlex.
- The CRISPR-Cas revolution in head and neck cancer: a new era of targeted therapy.Functional & integrative genomics · 2025Review
- BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target.Scientific reports · 2025Article
- Molecular pathological approach to cancer epigenomics and its clinical application.Pathology international · 2024Review
- PTEN deficiency potentiates HBV-associated liver cancer development through augmented GP73/GOLM1.Journal of translational medicine · 2024Article
- A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma.Oncology research · 2024Review
- Metastasis suppressor genes in clinical practice: are they druggable?Cancer metastasis reviews · 2023Review
- Article
- Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma.Asian journal of pharmaceutical sciences · 2023Review
- Genome-wide CRISPR knockout screening identified G protein pathway suppressor 2 as a novel tumor suppressor for uveal melanoma metastasis.Journal of cancer research and clinical oncology · 2023Article
- Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma.Clinical epigenetics · 2023Article
- Exploring liver cancer biology through functional genetic screens.Nature reviews. Gastroenterology & hepatology · 2021Review
- The potential prognostic values of the ADAMTS-like protein family: an integrative pan-cancer analysis.Annals of translational medicine · 2021Article
- ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment.Cancers · 2021Review
- Exploiting the CRISPR-Cas9 gene-editing system for human cancers and immunotherapy.Clinical & translational immunology · 2021Review
- Integrated Analyses Reveal the Multi-Omics and Prognostic Characteristics of ATP5B in Breast Cancer.Frontiers in genetics · 2021Article
- Optimizing sgRNA to Improve CRISPR/Cas9 Knockout Efficiency: Special Focus on Human and Animal Cell.Frontiers in bioengineering and biotechnology · 2021Review
- Article
- CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer.Frontiers in immunology · 2020Review
- Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis.BioMed research international · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeIt is important for hepatocellular carcinoma (HCC) treatment that the targets related to its progression are identified. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated nuclease 9 (Cas9)-based genetic screening is a powerful tool for identifying genes with loss-of-function mutations that are critical for tumour growth and metastasis.
methodsWe transduced the human SMMC7721 HCC cell line expressing Cas9 with a human genome-scale CRISPR-Cas9 knockout (GeCKO) lentiviral library A (hGeCKOa) of 65,383 single-guide RNAs (sgRNAs) targeting 19,050 human genes; we then subcutaneously transplanted the transduced cells into nude mice.
resultsThe transduced cells were found to proliferate and metastasize faster than the untransduced cells. Through next-generation sequencing, the genes potentially related to HCC proliferation and metastasis were identified. The sgRNAs targeting the ADAMTSL3 and PTEN genes appeared twice on the list of genes related to HCC proliferation and metastasis, respectively. Analysis based on the data mining of Oncomine revealed that the ADAMTSL3 and PTEN genes were expressed at lower levels in HCC cells than they were in normal liver cells, indicating their tumour-suppressive roles. Downregulation of ADAMTSL3 and PTEN displayed poor overall survival (OS) and predicted poor relapse-free survival (RFS), further supporting their tumour-suppressive roles. Moreover, knocking out either the ADAMTSL3 or PTEN genes promoted either the proliferation or metastasis of HCC cells, respectively.
conclusionsUsing both in vitro and in vivo approaches, we described the profound role of the ADAMTSL3 and PTEN genes. This study indicates novel candidate targets for use in HCC treatment and therapy.
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