A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site-specifically cleave DNA in the CRISPR/Cas9 system. Despite the high incidence of hepatocellular carcinoma (HCC), the patient’s outcome is poor. As a result of the emergence of therapeutic resistance in HCC patients, clinicians have faced difficulties in treating such tumor. In addition, CRISPR/Cas9 screens were used to identify genes that improve the clinical response of HCC patients. It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer, with a particular emphasis on HCC as part of the current state of knowledge. Thus, in order to locate recent developments in oncology research, we examined both the Scopus database and the PubMed database. The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs. Drug resistance can be overcome with the help of the CRISPR/Cas9 system. HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening, although this method is not without limitations. It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy. CRISPR and its applications to tumor research, particularly in HCC, are examined in this study through a review of the literature.

[1]  Zhongdang Xiao,et al.  Engineered extracellular vesicles mediated CRISPR-induced deficiency of IQGAP1/FOXM1 reverses sorafenib resistance in HCC by suppressing cancer stem cells , 2023, Journal of Nanobiotechnology.

[2]  Wanqiu Zhang,et al.  SQSTM1/p62 Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma , 2023, Cells.

[3]  Hongmei Zheng,et al.  CRISPR activation screening in a mouse model for drivers of hepatocellular carcinoma growth and metastasis , 2023, iScience.

[4]  Deniz M. Ozata,et al.  CRISPR‐induced exon skipping of β‐catenin reveals tumorigenic mutants driving distinct subtypes of liver cancer , 2023, The Journal of pathology.

[5]  Han Yang,et al.  Safeguarding genome integrity during gene-editing therapy in a mouse model of age-related macular degeneration , 2022, Nature communications.

[6]  C. C. Wong,et al.  Genome‐Wide CRISPR/Cas9 Library Screening Revealed Dietary Restriction of Glutamine in Combination with Inhibition of Pyruvate Metabolism as Effective Liver Cancer Treatment , 2022, Advanced science.

[7]  S. Qiu,et al.  Genome-Scale CRISPR screen identifies LAPTM5 driving lenvatinib resistance in hepatocellular carcinoma , 2022, Autophagy.

[8]  Chun-Ming Wong,et al.  In Vivo Genome-Wide CRISPR Activation Screening Identifies Functionally Important Long Noncoding RNAs in Hepatocellular Carcinoma , 2022, Cellular and molecular gastroenterology and hepatology.

[9]  D. Qujeq,et al.  CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer , 2022, Cellular & Molecular Biology Letters.

[10]  Yao Huang,et al.  Deubiquitinating enzyme JOSD2 promotes hepatocellular carcinoma progression through interacting with and inhibiting CTNNB1 degradation , 2022, Cell biology international.

[11]  Jun-jie Xu,et al.  CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway , 2022, Science China Life Sciences.

[12]  K. Qu,et al.  Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer , 2022, Protein & Cell.

[13]  M. Marz,et al.  A genome‐wide CRISPR activation screen reveals Hexokinase 1 as a critical factor in promoting resistance to multi‐kinase inhibitors in hepatocellular carcinoma cells , 2022, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  Xiaosong Rao,et al.  CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma , 2022, Molecular cancer.

[15]  Yu Chen,et al.  Ultrasound-Controlled CRISPR/Cas9 System Augments Sonodynamic Therapy of Hepatocellular Carcinoma , 2021, ACS Central Science.

[16]  Yong Peng,et al.  Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing , 2021, Molecular Cancer.

[17]  Hoi Yee Chu,et al.  A Combinatorial CRISPR–Cas9 Screen Identifies Ifenprodil as an Adjunct to Sorafenib for Liver Cancer Treatment , 2021, Cancer Research.

[18]  Yongyan Wu,et al.  Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer , 2021, Molecular cancer.

[19]  See-Hyoung Park,et al.  Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells , 2021, Journal of personalized medicine.

[20]  Y. Sang,et al.  Review of applications of CRISPR-Cas9 gene-editing technology in cancer research , 2021, Biological procedures online.

[21]  C. C. Wong,et al.  Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer , 2021, Cells.

[22]  Lijuan Duan,et al.  Nanoparticle Delivery of CRISPR/Cas9 for Genome Editing , 2021, Frontiers in Genetics.

[23]  P. Blancafort,et al.  Reprogramming the anti-tumor immune response via CRISPR genetic and epigenetic editing , 2021, Molecular therapy. Methods & clinical development.

[24]  Yong Ni,et al.  lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9 , 2021, Frontiers in Molecular Biosciences.

[25]  Bingran Yu,et al.  Charge-reversal nanocomolexes-based CRISPR/Cas9 delivery system for loss-of-function oncogene editing in hepatocellular carcinoma. , 2021, Journal of controlled release : official journal of the Controlled Release Society.

[26]  S. Yamaoka,et al.  Intrinsic activation of β-catenin signaling by CRISPR/Cas9-mediated exon skipping contributes to immune evasion in hepatocellular carcinoma , 2021, Scientific Reports.

[27]  H. Law,et al.  RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition , 2021, Cancer Cell International.

[28]  I. Ng,et al.  Genome-wide CRISPR-Cas9 knockout library screening identified PTPMT1 in cardiolipin synthesis is crucial to survival in hypoxia in liver cancer. , 2021, Cell reports.

[29]  Jingqing Le,et al.  Co-delivery of Sorafenib and CRISPR/Cas9 Based on Targeted Core-Shell Hollow Mesoporous Organosilica Nanoparticles for Synergistic HCC Therapy. , 2020, ACS applied materials & interfaces.

[30]  K. Schachtschneider,et al.  Generation of genetically tailored porcine liver cancer cells by CRISPR/Cas9 editing , 2020, BioTechniques.

[31]  Baohong Zhang CRISPR/Cas gene therapy , 2020, Journal of cellular physiology.

[32]  Bingran Yu,et al.  A Lactose‐Derived CRISPR/Cas9 Delivery System for Efficient Genome Editing In Vivo to Treat Orthotopic Hepatocellular Carcinoma , 2020, Advanced science.

[33]  P. Xie,et al.  TRAF3 Acts as a Checkpoint of B Cell Receptor Signaling to Control Antibody Class Switch Recombination and Anergy , 2020, The Journal of Immunology.

[34]  A. Shafei,et al.  lncRNA- RP11-156p1.3, novel diagnostic and therapeutic targeting via CRISPR/Cas9 editing in hepatocellular carcinoma. , 2020, Genomics.

[35]  J. Nielsen,et al.  Improvement in the Current Therapies for Hepatocellular Carcinoma Using a Systems Medicine Approach , 2020, Advanced biosystems.

[36]  R. Miftakhova,et al.  Therapeutic Editing of the TP53 Gene: Is CRISPR/Cas9 an Option? , 2020, Genes.

[37]  Keming Zhang,et al.  Genome-scale CRISPR activation screening identifies a role of LRP8 in Sorafenib resistance in Hepatocellular carcinoma. , 2020, Biochemical and biophysical research communications.

[38]  S. Roy,et al.  Assessment of risk factors, and racial and ethnic differences in hepatocellular carcinoma , 2020, JGH open : an open access journal of gastroenterology and hepatology.

[39]  Ruibin Li,et al.  Genome-wide CRISPR knockout screens identify ADAMTSL3 and PTEN genes as suppressors of HCC proliferation and metastasis, respectively , 2020, Journal of Cancer Research and Clinical Oncology.

[40]  末村 茂樹 CRISPR Loss-of-Function Screen Identifies the Hippo Signaling Pathway as the Mediator of Regorafenib Efficacy in Hepatocellular Carcinoma , 2020 .

[41]  W. Link,et al.  CRISPR/Cas9‐mediated genome editing: From basic research to translational medicine , 2020, Journal of cellular and molecular medicine.

[42]  J. Nault,et al.  The landscape of gene mutations in cirrhosis and hepatocellular carcinoma. , 2020, Journal of hepatology.

[43]  H. Nishina,et al.  Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma , 2020, Cancers.

[44]  Lei Yu,et al.  A tumor suppressor enhancing module orchestrated by GATA4 denotes a therapeutic opportunity for GATA4 deficient HCC patients , 2020, Theranostics.

[45]  Rolf Backofen,et al.  Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants , 2019, Nature Reviews Microbiology.

[46]  Fan Zhang,et al.  CRISPR/Cas9-mediated knockout of NSD1 suppresses the hepatocellular carcinoma development via the NSD1/H3/Wnt10b signaling pathway , 2019, Journal of Experimental & Clinical Cancer Research.

[47]  Jun-feng Wang,et al.  Long non-coding RNA RP11-468E2.5 curtails colorectal cancer cell proliferation and stimulates apoptosis via the JAK/STAT signaling pathway by targeting STAT5 and STAT6 , 2019, Journal of Experimental & Clinical Cancer Research.

[48]  K. Bissig,et al.  Using CRISPR/Cas9 to model human liver disease , 2019, JHEP reports.

[49]  I. Ng,et al.  Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC , 2019, Nature Communications.

[50]  Fei Li,et al.  Construction of Traf3 knockout liver cancer cell line using CRISPR/Cas9 system , 2019, Journal of cellular biochemistry.

[51]  Lingxian Meng,et al.  Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment , 2019, Clinical genetics.

[52]  B. Goh,et al.  Genome-wide CRISPR knockout screens identify NCAPG as an essential oncogene for hepatocellular carcinoma tumor growth , 2019, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[53]  P. Sun,et al.  The effect of CTCF binding sites destruction by CRISPR/Cas9 on transcription of metallothionein gene family in liver hepatocellular carcinoma. , 2019, Biochemical and biophysical research communications.

[54]  I. Melero,et al.  Cytokines in clinical cancer immunotherapy , 2018, British Journal of Cancer.

[55]  P. Komolmit,et al.  Immunotherapy for hepatocellular carcinoma treatment , 2018, Thai Journal of Hepatology.

[56]  Shiu-Feng Huang,et al.  AAV serotype 8-mediated liver specific GNMT expression delays progression of hepatocellular carcinoma and prevents carbon tetrachloride-induced liver damage , 2018, Scientific Reports.

[57]  Jennifer A. Doudna,et al.  CRISPR-Cas guides the future of genetic engineering , 2018, Science.

[58]  Yue Zhang,et al.  CRISPR/Cas9-mediated hypoxia inducible factor-1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma , 2018, Oncology reports.

[59]  Ji Hyun Lee,et al.  Selective targeting of KRAS oncogenic alleles by CRISPR/Cas9 inhibits proliferation of cancer cells , 2018, Scientific Reports.

[60]  G. Venkataraman,et al.  CRISPR for Crop Improvement: An Update Review , 2018, Front. Plant Sci..

[61]  L. Ratner,et al.  The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30II and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma. , 2018, Virology.

[62]  S. Duan,et al.  Unlockable Nanocomplexes with Self‐Accelerating Nucleic Acid Release for Effective Staged Gene Therapy of Cardiovascular Diseases , 2018, Advanced materials.

[63]  Z. Liao,et al.  CRISPR/Cas9‐mediated knockout of HBsAg inhibits proliferation and tumorigenicity of HBV‐positive hepatocellular carcinoma cells , 2018, Journal of cellular biochemistry.

[64]  Lisa Tucker-Kellogg,et al.  Combination Therapy and the Evolution of Resistance: The Theoretical Merits of Synergism and Antagonism in Cancer. , 2018, Cancer research.

[65]  Yanmin Zhang,et al.  Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer , 2018, Advanced science.

[66]  Z. Zeng,et al.  LncRNAs regulate the cytoskeleton and related Rho/ROCK signaling in cancer metastasis , 2018, Molecular Cancer.

[67]  Xiaoling Yu,et al.  Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment , 2018, Medicinal research reviews.

[68]  Haiyang Xie,et al.  Genome-wide CRISPR screen reveals SGOL1 as a druggable target of sorafenib-treated hepatocellular carcinoma , 2018, Laboratory Investigation.

[69]  J. Joung,et al.  Gene therapy comes of age , 2018, Science.

[70]  Jerilyn A Timlin,et al.  Delivering CRISPR: a review of the challenges and approaches , 2018, Drug delivery.

[71]  C. Pirker,et al.  Dynamics of CRISPR/Cas9-mediated genomic editing of the AXL locus in hepatocellular carcinoma cells. , 2017, Oncology letters.

[72]  Denise Serra,et al.  CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma. , 2017, Gastroenterology.

[73]  Lingyi Chen,et al.  Simple Meets Single: The Application of CRISPR/Cas9 in Haploid Embryonic Stem Cells , 2017, Stem cells international.

[74]  Giulliana Augusta Rangel Gonçalves,et al.  Gene therapy: advances, challenges and perspectives , 2017, Einstein.

[75]  Dexi Liu,et al.  CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice , 2017, Cancer biology & therapy.

[76]  M. Kudo,et al.  Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update , 2017, Hepatology International.

[77]  A. Jayachandran,et al.  Seek and destroy: targeted adeno-associated viruses for gene delivery to hepatocellular carcinoma , 2017, Drug delivery.

[78]  S. Pipe New therapies for hemophilia. , 2016, Hematology. American Society of Hematology. Education Program.

[79]  F. D. De Braud,et al.  Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions. , 2016, Cancer discovery.

[80]  S. Imbeaud,et al.  Genotype‐phenotype correlation of CTNNB1 mutations reveals different ß‐catenin activity associated with liver tumor progression , 2016, Hepatology.

[81]  R. Yeung,et al.  Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma , 2016, Pediatric blood & cancer.

[82]  G. Bishop,et al.  Nuclear TRAF3 is a negative regulator of CREB in B cells , 2016, Proceedings of the National Academy of Sciences.

[83]  S. Rodríguez-Perales,et al.  CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling , 2015, International journal of molecular sciences.

[84]  Clifford A. Meyer,et al.  Sequence determinants of improved CRISPR sgRNA design , 2015, Genome research.

[85]  Shao-Cong Sun,et al.  Targeting signaling factors for degradation, an emerging mechanism for TRAF functions , 2015, Immunological reviews.

[86]  G. Bishop,et al.  TRAF3, ubiquitination, and B‐lymphocyte regulation , 2015, Immunological reviews.

[87]  Denise Rizzolo,et al.  Managing localized unresectable hepatocellular carcinoma , 2015, JAAPA : official journal of the American Academy of Physician Assistants.

[88]  J. Doudna,et al.  The new frontier of genome engineering with CRISPR-Cas9 , 2014, Science.

[89]  R. Chai,et al.  Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells , 2014, Bioscience reports.

[90]  F. Zhang,et al.  CRISPR/Cas9 for genome editing: progress, implications and challenges. , 2014, Human molecular genetics.

[91]  M. Spalding,et al.  TALEN-mediated genome editing: prospects and perspectives. , 2014, The Biochemical journal.

[92]  M. Jinek,et al.  Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease , 2014, Nature.

[93]  L. Marraffini,et al.  Harnessing CRISPR-Cas9 immunity for genetic engineering. , 2014, Current opinion in microbiology.

[94]  Shuhan Sun,et al.  A long noncoding RNA activated by TGF-β promotes the invasion-metastasis cascade in hepatocellular carcinoma. , 2014, Cancer cell.

[95]  Jennifer A. Doudna,et al.  DNA interrogation by the CRISPR RNA-guided endonuclease Cas9 , 2014, Nature.

[96]  Neville E. Sanjana,et al.  Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells , 2014, Science.

[97]  G. Bishop,et al.  A Complex Relationship between TRAF3 and Non-Canonical NF-κB2 Activation in B Lymphocytes , 2013, Front. Immunol..

[98]  E. Lander,et al.  Genetic Screens in Human Cells Using the CRISPR-Cas9 System , 2013, Science.

[99]  M. Lazar,et al.  Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARγ , 2013, Proceedings of the National Academy of Sciences.

[100]  G. Church,et al.  CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering , 2013, Nature Biotechnology.

[101]  C. Barbas,et al.  ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. , 2013, Trends in biotechnology.

[102]  Gary L. Gallia,et al.  TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal , 2013, Proceedings of the National Academy of Sciences.

[103]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[104]  J. Keith Joung,et al.  TALENs: a widely applicable technology for targeted genome editing , 2012, Nature Reviews Molecular Cell Biology.

[105]  D. Voytas,et al.  Efficient TALEN-mediated gene knockout in livestock , 2012, Proceedings of the National Academy of Sciences.

[106]  J. Doudna,et al.  A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity , 2012, Science.

[107]  Ying-Ju Chen,et al.  Replicating retroviral vectors for oncolytic virotherapy of experimental hepatocellular carcinoma. , 2012, Oncology reports.

[108]  Dania Daye,et al.  Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. , 2012, Seminars in cell & developmental biology.

[109]  S. Choo,et al.  Targeted Therapy in Hepatocellular Carcinoma , 2011, International journal of hepatology.

[110]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[111]  G. Bishop,et al.  TNF Receptor-Associated Factor 3 Is Required for T Cell-Mediated Immunity and TCR/CD28 Signaling , 2011, The Journal of Immunology.

[112]  J. Bruix,et al.  A meta‐analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma , 2010, Hepatology.

[113]  Kathryn A. O’Donnell,et al.  Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model , 2009, Cell.

[114]  L. Cantley,et al.  Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation , 2009, Science.

[115]  Y. Tesfaigzi,et al.  How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? , 2009, Cell cycle.

[116]  R. Epstein,et al.  Evolution of systemic therapy of advanced hepatocellular carcinoma. , 2008, World journal of gastroenterology.

[117]  J. Keats,et al.  Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling , 2008, Nature Immunology.

[118]  J. Orange,et al.  Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases , 2008, Nature Biotechnology.

[119]  G. Cheng,et al.  Rescue of TRAF3-null mice by p100 NF-κB deficiency , 2006, The Journal of experimental medicine.

[120]  Deanna Cross,et al.  Gene therapy for cancer treatment: past, present and future. , 2006, Clinical medicine & research.

[121]  E. Harhaj,et al.  Regulation of the NF-κB-inducing Kinase by Tumor Necrosis Factor Receptor-associated Factor 3-induced Degradation* , 2004, Journal of Biological Chemistry.

[122]  M. Colombo Epidemiology of hepatocellular carcinoma. , 1995, The Italian journal of gastroenterology.

[123]  R. Mulligan,et al.  The basic science of gene therapy. , 1993, Science.

[124]  D. Voytas,et al.  In vivo genome editing using a high-efficiency TALEN system , 2020 .

[125]  Biao Chen Role of long noncoding RNAs in hepatocellular carcinoma , 2014 .

[126]  이연수 Functional genomics reveal that the serine synthesis pathway is essential in breast cancer , 2011 .

[127]  Barry Halliwell,et al.  Oxidative stress and cancer: have we moved forward? , 2007, The Biochemical journal.

[128]  F. X. Bosch,et al.  Epidemiology of Primary Liver Cancer , 1999, Seminars in liver disease.

[129]  D. Woodfield Hepatocellular carcinoma. , 1986, The New Zealand medical journal.