CRISPR/Cas9基因编辑技术在前列腺癌研究中的进展
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摘要
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9)基因编辑技术是基于细菌和古细菌适应性免疫防御系统发展而来的一种基因编辑工具。Cas9蛋白借助gRNA的引导靶向目标基因进而实现对目标基因精确、高效的编辑。因其具有操作简单、成本低的特点,被研究人员广泛应用,并在前列腺癌相关基因及信号通路的研究中发挥着重要作用。该文将对CRISPR/Cas9基因编辑技术的发展、作用机理及其在前列腺癌研究中的应用进展进行综述。
CRISPR/Cas9(clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9)technology is a gene editing tool based on the development of bacterial and archaeal adaptive immune defense systems. The Cas9 protein targets the gene by gRNA guidance to achieve accurate and efficient editing of the target genes. Because of its simple operation and low cost, it is widely used and plays an important role in the research of prostate cancer related genes and signaling pathways. Here, we briefly introduce the development process and mechanism of the CRISPR/Cas9 as well as summarize its application in the research of prostate cancer.
CRISPR/Cas9(clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9)technology is a gene editing tool based on the development of bacterial and archaeal adaptive immune defense systems. The Cas9 protein targets the gene by gRNA guidance to achieve accurate and efficient editing of the target genes. Because of its simple operation and low cost, it is widely used and plays an important role in the research of prostate cancer related genes and signaling pathways. Here, we briefly introduce the development process and mechanism of the CRISPR/Cas9 as well as summarize its application in the research of prostate cancer.
引文
[1]Bhakta MS,Henry IM,Ousterout DG,et al.Highly active zinc-finger nucleases by extended modular assembly.Genome Res,2013,23:530-8
[2]Joung JK,Sander JD.TALENs:a widely applicable technology for targeted genome editing.Nat Rev Mol Cell Biol,2013,14:49-55
[3]Sakuma T,Woltjen K.Nuclease-mediated genome editing:at the front-line of functional genomics technology.Dev Growth Differ,2014,56:2-13
[4]Schokrpur S,Hu J,Moughon DL,et al.CRISPR-mediated VHL knockout generates an improved model for metastatic renal cell carcinoma.Sci Rep,2016,6:29032
[5]Annunziato S,Kas SM,Nethe M,et al.Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.Genes Dev,2016,30:1470-80
[6]Zuckermann M,Hovestadt V,Knobbe-Thomsen CB,et al.Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.Nat Commun,2015,6:7391
[7]Wallace J,Hu R,Mosbruger TL,et al.Genome-wide CRISPR-Cas9 screen identifies microRNAs that regulate myeloid leukemia cell growth.PLoS One,2016,11:e0153689
[8]Kim MY,Yu KR,Kenderian SS,et al.Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T cell immunotherapy for acute myeloid leukemia.Cell,2018,173:1439-53.e19
[9]Euquem J,Mansilla-Soto J,Giavridis T,et al.Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection.Nature,2017,543:113-7
[10]Ishino Y,Shinagawa H,Makino K,et al.Nucleotide sequence of the iap gene,responsible for alkaline phosphatase isozyme conversion in Escherichia coli,and identification of the gene product.J Bacteriol,1987,169:5429-33
[11]Mojica FJ,Diez-villasenor C,Garcia-Martinez J,et al.Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements.J Mol Evol,2005,60:174-82
[12]Bolotin A,Quinquis B,Sorokin A,et al.Clustered regularly interspaced short palindrome repeats(CRISPRs)have spacers of extrachromosomal origin.Microbiology,2005,151:2551-61
[13]Barrangou R,Fremaux C,Deveau H,et al.CRISPRprovides acquired resistance against viruses in prokaryotes.Science,2007,315:1709-12
[14]Brouns SJ,Jore MM,Lundren M,et al.Small CRISPRRNAs guide antiviral defense in prokaryotes.Science,2008,321:960-4
[15]Deltcheva E,Chylinski K,Sharma CM,et al.CRISPRRNA maturation by trans-encoded small RNA and host factor RNase III.Nature,2011,471:602-7
[16]Jinek M,Chylinski K,Fonfara I,et al.A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.Science,2012,337:816-21
[17]Cong L,RanF A,Cox D,et al.Multiplex genome engineering using CRISPR/Cas systems.Science,2013,339:819-23
[18]Mali P,Yang L,Esvert KM,et al.RNA-guided human genome engineering via Cas9.Science,2013,339:823-6
[19]Qi LS,Larson MH,Gilbert LA,et al.Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.Cell,2013,152:1173-83
[20]Kampmann M.CRISPRi and CRISPRa screens in mammalian cells for precision biology and medicine.ACSChem Biol,2018,13:406-16
[21]Makarova KS,Haft DH,Barrangou R,et al.Evolution and classification of the CRISPR-Cas systems.Nat Rev Microbiol,2011,9:467-77
[22]Spiman M,Cocozaki A,Hale C,et al.Structure of an RNA silencing complex of the CRISPR-Cas immune system.Mol Cell,2013,52:146-52
[23]Heidrich N,Vogel J.Same same but different:new structural insight into CRISPR-Cas complexes.Mol Cell,2013,52:4-7
[24]Gottesman S.Microbiology:dicing defence in bacteria.Nature,2011,471:588-9
[25]Haurwitz RE,Jinek M,Widenheft B,et al.Sequence-and structure-specific RNA processing by a CRISPR endonuclease.Science,2010,329:1355-8
[26]Sapranauskas R,Gasiunas G,Fremaux C,et al.The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli.Nucleic Acids Res,2011,39:9275-82
[27]Rath D,Amlinger L,Rath A,et al.The CRISPR-Cas immune system:biology,mechanisms and applications.Biochimie,2015,117:119-28
[28]Garneau JE,Dupuis ME,Villion NM,et al.The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA.Nature,2010,468:67-71
[29]Sternberg SH,Redding S,Jinek M,et al.DNAinterrogation by the CRISPR RNA-guided endonuclease Cas9.Nature,2014,507:62-7
[30]Symington LS,Gautier J.Double-strand break end resection and repair pathway choice.Annu Rev Genet,2011,45:247-71
[31]Ran FA,Hsu PD,Wright J,et al.Genome engineering using the CRISPR-Cas9 system.Nat Protoc,2013,8:2281-308
[32]Torre LA,Bray F,Sieget RL,et al.Global cancer statistics,2012.CA Cancer J Clin,2015,65:87-108
[33]Chen CD,Welsbie DS,Tran C,et al.Molecular determinants of resistance to antiandrogen therapy.Nat Med,2004,10:33-9
[34]Harris WP,Mostaghel EA,Nelson PS,et al.Androgen deprivation therapy:progress in understanding mechanisms of resistance and optimizing androgen depletion.Nat Clin Pract Urol,2009,6:76-85
[35]Wei C,Wang F,Liu W,et al.CRISPR/Cas9 targeting of the androgen receptor suppresses the growth of LNCaPhuman prostate cancer cells.Mol Med Rep,2018,17:2901-6
[36]Liu XS,Brown M,Hoy JJ,et al.Inhibition of androgen receptor promotes CXC-chemokine receptor 7-mediated prostate cancer cell survival.Sci Rep,2017,7:3058
[37]Yin Y,Xu L,Chang Y,et al.N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421/ATM pathway.Mol Cancer,2019,18:11
[38]Mimeault M,Batra SK.Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer-and metastasis-initiating cells.JCell Mol Med,2013,17:30-54
[39]Maina PK,Shao P,Jia X,et al.Histone demethylase PHF8regulates hypoxia signaling through HIF1αand H3K4me3.Biochim Biophys Acta,2017,1860:1002-12
[40]Damaghi M,Wojtkowiak JW,Gilles RJ.pH sensing and regulation in cancer.Front Physiol,2013,4:370
[41]Chen B,Liu J,Ho TT,et al.ERK-mediated NF-κBactivation through ASIC1 in response to acidosis.Oncogenesis,2016,5:e279
[42]Beaver LM,Kuintzle R,Buchanan A,et al.Long noncoding RNAs and sulforaphane:a target for chemoprevention and suppression of prostate cancer.J Nutr Biochem,2017,42:72-83
[43]Shukla S,Zhang X,Niknafs YS,et al.Identification and validation of PCAT14 as prognostic biomarker in prostate cancer.Neoplasia,2016,18:489-99
[44]Xiao G,Yao J,Kong D,et al.The long noncoding RNATTTY15,which is located on the Y chromosome,promotes prostate cancer progression by sponging let-7.Eur Urol,2018[Epub ahead of print]
[45]Zhang P,Xia JH,Zhu J,et al.High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing.Nat Commun,2018,9:2022
[46]Zhou J,Yu Y,Zhu A,et al.Meta-analysis of association between rs1447295 polymorphism and prostate cancer susceptibility.Oncotarget,2017,8:67029-42
[47]Luo Z,Rhie SK,Lay FD,et al.A Prostate cancer risk element functions as a repressive loop that regulates HOXA13.Cell Rep,2017,21:1411-7
[48]Jin HJ,Jung S,Debroy AR,et al.Identification and validation of regulatory SNPs that modulate transcription factor chromatin binding and gene expression in prostate cancer.Oncotarget,2016,7:54616-26
[49]Kaufmann O,Volmerig J,Dietel M.Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas.Am J Clin Pathol,2000,113:683-7
[50]Gao P,Xia JH,Sipeky C,et al.Biology and clinical implications of the 19q13 aggressive prostate cancer susceptibility locus.Cell,2018,174:576-89.e18
[51]Spisak S,Lawrenson K,Fu Y,et al.CAUSEL:an epigenome-and genome-editing pipeline for establishing function of noncoding GWAS variants.Nat Med,2015,21:1357-63
[52]Cho SW,Kim S,Kim Y,et al.Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases.Genome Res,2014,24:132-41
[53]Kleinstiver BP,Pattanayak V,Prew MS,et al.Highfidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.Nature,2016,529:490-5
[54]Slaymaker IM,Gao L,Zetzche B,et al.Rationally engineered Cas9 nucleases with improved specificity.Science,2016,351:84-8
[55]Kleinstiver BP,Tsai SQ,Prew MS,et al.Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells.Nat Biotechnol,2016,34:869-74
[56]Ran FA,Cong L,Yan WX,et al.In vivo genome editing using Staphylococcus aureus Cas9.Nature,2015,520:186-91
[57]Yin H,Song CQ,Dorkin JR,et al.Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.Nat Biotechnol,2016,34:328-33
[58]Kretzmann JA,Ho D,Evans CW,et al.Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA.Chem Sci,2017,8:2923-30
[59]Zhen S,Takahashi Y,Narita S,et al.Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome.Oncotarget,2017,8:9375-87
[60]Guo Y,Perez AA,Hazelett DJ,et al.CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops.Genome Biol,2018,19:160
[61]GuoX,Dean A.CRISPR/Cas9 offers a new tool for studying the role of chromatin architecture in disease pathogenesis.Genome Biol,2018,19:185
[2]Joung JK,Sander JD.TALENs:a widely applicable technology for targeted genome editing.Nat Rev Mol Cell Biol,2013,14:49-55
[3]Sakuma T,Woltjen K.Nuclease-mediated genome editing:at the front-line of functional genomics technology.Dev Growth Differ,2014,56:2-13
[4]Schokrpur S,Hu J,Moughon DL,et al.CRISPR-mediated VHL knockout generates an improved model for metastatic renal cell carcinoma.Sci Rep,2016,6:29032
[5]Annunziato S,Kas SM,Nethe M,et al.Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.Genes Dev,2016,30:1470-80
[6]Zuckermann M,Hovestadt V,Knobbe-Thomsen CB,et al.Somatic CRISPR/Cas9-mediated tumour suppressor disruption enables versatile brain tumour modelling.Nat Commun,2015,6:7391
[7]Wallace J,Hu R,Mosbruger TL,et al.Genome-wide CRISPR-Cas9 screen identifies microRNAs that regulate myeloid leukemia cell growth.PLoS One,2016,11:e0153689
[8]Kim MY,Yu KR,Kenderian SS,et al.Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T cell immunotherapy for acute myeloid leukemia.Cell,2018,173:1439-53.e19
[9]Euquem J,Mansilla-Soto J,Giavridis T,et al.Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection.Nature,2017,543:113-7
[10]Ishino Y,Shinagawa H,Makino K,et al.Nucleotide sequence of the iap gene,responsible for alkaline phosphatase isozyme conversion in Escherichia coli,and identification of the gene product.J Bacteriol,1987,169:5429-33
[11]Mojica FJ,Diez-villasenor C,Garcia-Martinez J,et al.Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements.J Mol Evol,2005,60:174-82
[12]Bolotin A,Quinquis B,Sorokin A,et al.Clustered regularly interspaced short palindrome repeats(CRISPRs)have spacers of extrachromosomal origin.Microbiology,2005,151:2551-61
[13]Barrangou R,Fremaux C,Deveau H,et al.CRISPRprovides acquired resistance against viruses in prokaryotes.Science,2007,315:1709-12
[14]Brouns SJ,Jore MM,Lundren M,et al.Small CRISPRRNAs guide antiviral defense in prokaryotes.Science,2008,321:960-4
[15]Deltcheva E,Chylinski K,Sharma CM,et al.CRISPRRNA maturation by trans-encoded small RNA and host factor RNase III.Nature,2011,471:602-7
[16]Jinek M,Chylinski K,Fonfara I,et al.A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.Science,2012,337:816-21
[17]Cong L,RanF A,Cox D,et al.Multiplex genome engineering using CRISPR/Cas systems.Science,2013,339:819-23
[18]Mali P,Yang L,Esvert KM,et al.RNA-guided human genome engineering via Cas9.Science,2013,339:823-6
[19]Qi LS,Larson MH,Gilbert LA,et al.Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression.Cell,2013,152:1173-83
[20]Kampmann M.CRISPRi and CRISPRa screens in mammalian cells for precision biology and medicine.ACSChem Biol,2018,13:406-16
[21]Makarova KS,Haft DH,Barrangou R,et al.Evolution and classification of the CRISPR-Cas systems.Nat Rev Microbiol,2011,9:467-77
[22]Spiman M,Cocozaki A,Hale C,et al.Structure of an RNA silencing complex of the CRISPR-Cas immune system.Mol Cell,2013,52:146-52
[23]Heidrich N,Vogel J.Same same but different:new structural insight into CRISPR-Cas complexes.Mol Cell,2013,52:4-7
[24]Gottesman S.Microbiology:dicing defence in bacteria.Nature,2011,471:588-9
[25]Haurwitz RE,Jinek M,Widenheft B,et al.Sequence-and structure-specific RNA processing by a CRISPR endonuclease.Science,2010,329:1355-8
[26]Sapranauskas R,Gasiunas G,Fremaux C,et al.The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli.Nucleic Acids Res,2011,39:9275-82
[27]Rath D,Amlinger L,Rath A,et al.The CRISPR-Cas immune system:biology,mechanisms and applications.Biochimie,2015,117:119-28
[28]Garneau JE,Dupuis ME,Villion NM,et al.The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA.Nature,2010,468:67-71
[29]Sternberg SH,Redding S,Jinek M,et al.DNAinterrogation by the CRISPR RNA-guided endonuclease Cas9.Nature,2014,507:62-7
[30]Symington LS,Gautier J.Double-strand break end resection and repair pathway choice.Annu Rev Genet,2011,45:247-71
[31]Ran FA,Hsu PD,Wright J,et al.Genome engineering using the CRISPR-Cas9 system.Nat Protoc,2013,8:2281-308
[32]Torre LA,Bray F,Sieget RL,et al.Global cancer statistics,2012.CA Cancer J Clin,2015,65:87-108
[33]Chen CD,Welsbie DS,Tran C,et al.Molecular determinants of resistance to antiandrogen therapy.Nat Med,2004,10:33-9
[34]Harris WP,Mostaghel EA,Nelson PS,et al.Androgen deprivation therapy:progress in understanding mechanisms of resistance and optimizing androgen depletion.Nat Clin Pract Urol,2009,6:76-85
[35]Wei C,Wang F,Liu W,et al.CRISPR/Cas9 targeting of the androgen receptor suppresses the growth of LNCaPhuman prostate cancer cells.Mol Med Rep,2018,17:2901-6
[36]Liu XS,Brown M,Hoy JJ,et al.Inhibition of androgen receptor promotes CXC-chemokine receptor 7-mediated prostate cancer cell survival.Sci Rep,2017,7:3058
[37]Yin Y,Xu L,Chang Y,et al.N-Myc promotes therapeutic resistance development of neuroendocrine prostate cancer by differentially regulating miR-421/ATM pathway.Mol Cancer,2019,18:11
[38]Mimeault M,Batra SK.Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer-and metastasis-initiating cells.JCell Mol Med,2013,17:30-54
[39]Maina PK,Shao P,Jia X,et al.Histone demethylase PHF8regulates hypoxia signaling through HIF1αand H3K4me3.Biochim Biophys Acta,2017,1860:1002-12
[40]Damaghi M,Wojtkowiak JW,Gilles RJ.pH sensing and regulation in cancer.Front Physiol,2013,4:370
[41]Chen B,Liu J,Ho TT,et al.ERK-mediated NF-κBactivation through ASIC1 in response to acidosis.Oncogenesis,2016,5:e279
[42]Beaver LM,Kuintzle R,Buchanan A,et al.Long noncoding RNAs and sulforaphane:a target for chemoprevention and suppression of prostate cancer.J Nutr Biochem,2017,42:72-83
[43]Shukla S,Zhang X,Niknafs YS,et al.Identification and validation of PCAT14 as prognostic biomarker in prostate cancer.Neoplasia,2016,18:489-99
[44]Xiao G,Yao J,Kong D,et al.The long noncoding RNATTTY15,which is located on the Y chromosome,promotes prostate cancer progression by sponging let-7.Eur Urol,2018[Epub ahead of print]
[45]Zhang P,Xia JH,Zhu J,et al.High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing.Nat Commun,2018,9:2022
[46]Zhou J,Yu Y,Zhu A,et al.Meta-analysis of association between rs1447295 polymorphism and prostate cancer susceptibility.Oncotarget,2017,8:67029-42
[47]Luo Z,Rhie SK,Lay FD,et al.A Prostate cancer risk element functions as a repressive loop that regulates HOXA13.Cell Rep,2017,21:1411-7
[48]Jin HJ,Jung S,Debroy AR,et al.Identification and validation of regulatory SNPs that modulate transcription factor chromatin binding and gene expression in prostate cancer.Oncotarget,2016,7:54616-26
[49]Kaufmann O,Volmerig J,Dietel M.Uroplakin III is a highly specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas.Am J Clin Pathol,2000,113:683-7
[50]Gao P,Xia JH,Sipeky C,et al.Biology and clinical implications of the 19q13 aggressive prostate cancer susceptibility locus.Cell,2018,174:576-89.e18
[51]Spisak S,Lawrenson K,Fu Y,et al.CAUSEL:an epigenome-and genome-editing pipeline for establishing function of noncoding GWAS variants.Nat Med,2015,21:1357-63
[52]Cho SW,Kim S,Kim Y,et al.Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases.Genome Res,2014,24:132-41
[53]Kleinstiver BP,Pattanayak V,Prew MS,et al.Highfidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.Nature,2016,529:490-5
[54]Slaymaker IM,Gao L,Zetzche B,et al.Rationally engineered Cas9 nucleases with improved specificity.Science,2016,351:84-8
[55]Kleinstiver BP,Tsai SQ,Prew MS,et al.Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells.Nat Biotechnol,2016,34:869-74
[56]Ran FA,Cong L,Yan WX,et al.In vivo genome editing using Staphylococcus aureus Cas9.Nature,2015,520:186-91
[57]Yin H,Song CQ,Dorkin JR,et al.Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo.Nat Biotechnol,2016,34:328-33
[58]Kretzmann JA,Ho D,Evans CW,et al.Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA.Chem Sci,2017,8:2923-30
[59]Zhen S,Takahashi Y,Narita S,et al.Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome.Oncotarget,2017,8:9375-87
[60]Guo Y,Perez AA,Hazelett DJ,et al.CRISPR-mediated deletion of prostate cancer risk-associated CTCF loop anchors identifies repressive chromatin loops.Genome Biol,2018,19:160
[61]GuoX,Dean A.CRISPR/Cas9 offers a new tool for studying the role of chromatin architecture in disease pathogenesis.Genome Biol,2018,19:185
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