• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

CRISPR/Cas9 筛选用于在癌细胞中全基因组研究 MYC 结合的 E 盒的必需性。

CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells.

机构信息

Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland.

Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznań, Poland.

出版信息

Mol Oncol. 2023 Nov;17(11):2295-2313. doi: 10.1002/1878-0261.13493. Epub 2023 Aug 7.

DOI:10.1002/1878-0261.13493
PMID:37519063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10620128/
Abstract

The transcription factor MYC is a proto-oncogene with a well-documented essential role in the pathogenesis and maintenance of several types of cancer. MYC binds to specific E-box sequences in the genome to regulate gene expression in a cell-type- and developmental-stage-specific manner. To date, a combined analysis of essential MYC-bound E-boxes and their downstream target genes important for growth of different types of cancer is missing. In this study, we designed a CRISPR/Cas9 library to destroy E-box sequences in a genome-wide fashion. In parallel, we used the Brunello library to knock out protein-coding genes. We performed high-throughput screens with these libraries in four MYC-dependent cancer cell lines-K562, ST486, HepG2, and MCF7-which revealed several essential E-boxes and genes. Among them, we pinpointed crucial common and cell-type-specific MYC-regulated genes involved in pathways associated with cancer development. Extensive validation of our approach confirmed that E-box disruption affects MYC binding, target-gene expression, and cell proliferation in vitro as well as tumor growth in vivo. Our unique, well-validated tool opens new possibilities to gain novel insights into MYC-dependent vulnerabilities in cancer cells.

摘要

转录因子 MYC 是一种原癌基因，在多种癌症的发病机制和维持中具有明确的重要作用。MYC 结合基因组中的特定 E 盒序列，以细胞类型和发育阶段特异性的方式调节基因表达。迄今为止，对不同类型癌症生长重要的必需 MYC 结合 E 盒及其下游靶基因的综合分析尚不存在。在这项研究中，我们设计了一个 CRISPR/Cas9 文库，以在全基因组范围内破坏 E 盒序列。同时，我们使用 Brunello 文库敲除编码蛋白的基因。我们在四个依赖 MYC 的癌细胞系（K562、ST486、HepG2 和 MCF7）中进行了这些文库的高通量筛选，揭示了几个必需的 E 盒和基因。其中，我们确定了与癌症发展相关途径中涉及的关键共同和细胞类型特异性 MYC 调节基因。对我们方法的广泛验证证实，E 盒的破坏会影响 MYC 结合、靶基因表达和体外细胞增殖以及体内肿瘤生长。我们独特的、经过良好验证的工具为深入了解癌细胞中依赖 MYC 的脆弱性提供了新的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/e1df8604d43e/MOL2-17-2295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/c69f3b2c746e/MOL2-17-2295-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/781d0b4c69a2/MOL2-17-2295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/0ef7bd9faeea/MOL2-17-2295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/6699b655c378/MOL2-17-2295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/674fdf1d8e42/MOL2-17-2295-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/e1df8604d43e/MOL2-17-2295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/c69f3b2c746e/MOL2-17-2295-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/781d0b4c69a2/MOL2-17-2295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/0ef7bd9faeea/MOL2-17-2295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/6699b655c378/MOL2-17-2295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/674fdf1d8e42/MOL2-17-2295-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690e/10620128/e1df8604d43e/MOL2-17-2295-g004.jpg

相似文献

1
CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells.CRISPR/Cas9 筛选用于在癌细胞中全基因组研究 MYC 结合的 E 盒的必需性。
Mol Oncol. 2023 Nov;17(11):2295-2313. doi: 10.1002/1878-0261.13493. Epub 2023 Aug 7.
2
Evaluation of myc E-box phylogenetic footprints in glycolytic genes by chromatin immunoprecipitation assays.通过染色质免疫沉淀试验评估糖酵解基因中的myc E盒系统发育足迹。
Mol Cell Biol. 2004 Jul;24(13):5923-36. doi: 10.1128/MCB.24.13.5923-5936.2004.
3
Identification of the HECT E3 ligase UBR5 as a regulator of MYC degradation using a CRISPR/Cas9 screen.利用 CRISPR/Cas9 筛选鉴定 HECT E3 连接酶 UBR5 作为 MYC 降解的调节剂。
Sci Rep. 2020 Nov 18;10(1):20044. doi: 10.1038/s41598-020-76960-z.
4
Tracing MYC Expression for Small Molecule Discovery.追踪 MYC 表达以发现小分子。
Cell Chem Biol. 2019 May 16;26(5):699-710.e6. doi: 10.1016/j.chembiol.2019.02.007. Epub 2019 Mar 14.
5
Do products of the myc proto-oncogene play a role in transcriptional regulation of the prothymosin alpha gene?原癌基因myc的产物在胸腺素α原基因的转录调控中起作用吗？
Mol Cell Biol. 1995 Dec;15(12):6999-7009. doi: 10.1128/MCB.15.12.6999.
6
SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF.SNHG15 是一个双功能的 MYC 调控的非编码基因座，编码一个长非编码 RNA，通过与 AIF 相互作用促进结直肠癌细胞的增殖、侵袭和耐药性。
J Exp Clin Cancer Res. 2019 Apr 24;38(1):172. doi: 10.1186/s13046-019-1169-0.
7
Genomic targets of the human c-Myc protein.人类c-Myc蛋白的基因组靶点。
Genes Dev. 2003 May 1;17(9):1115-29. doi: 10.1101/gad.1067003. Epub 2003 Apr 14.
8
Upstream stimulatory factor but not c-Myc enhances transcription of the human polymeric immunoglobulin receptor gene.上游刺激因子而非c-Myc增强人多聚免疫球蛋白受体基因的转录。
Mol Immunol. 2004 Jan;40(10):695-708. doi: 10.1016/j.molimm.2003.09.004.
9
A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts.一项旨在鉴定能挽救c-myc基因缺失的成纤维细胞生长缓慢表型的基因的遗传筛选。
Oncogene. 2000 Jul 6;19(29):3330-4. doi: 10.1038/sj.onc.1203639.
10
Expression of the TAF4b gene is induced by MYC through a non-canonical, but not canonical, E-box which contributes to its specific response to MYC.TAF4b基因的表达由MYC通过一个非经典而非经典的E盒诱导，这有助于其对MYC的特异性反应。
Int J Oncol. 2008 Dec;33(6):1271-80.

引用本文的文献

1
Comparative Analysis of Methods for Assessing On-Target Gene Editing Efficiencies.评估靶向基因编辑效率方法的比较分析
Methods Protoc. 2025 Mar 1;8(2):23. doi: 10.3390/mps8020023.
2
AZIN1 level is increased in medulloblastoma and correlates with c-Myc activity and tumor phenotype.髓母细胞瘤中AZIN1水平升高，且与c-Myc活性和肿瘤表型相关。
J Exp Clin Cancer Res. 2025 Feb 17;44(1):56. doi: 10.1186/s13046-025-03274-1.
3
Genetic advancements in breast cancer treatment: a review.乳腺癌治疗中的遗传学进展：综述

本文引用的文献

1
The lncRNA KTN1-AS1 co-regulates a variety of Myc-target genes and enhances proliferation of Burkitt lymphoma cells.长链非编码 RNA KTN1-AS1 共同调控多种 Myc 靶基因，并增强 Burkitt 淋巴瘤细胞的增殖。
Hum Mol Genet. 2022 Dec 16;31(24):4193-4206. doi: 10.1093/hmg/ddac159.
2
UALCAN: An update to the integrated cancer data analysis platform.UALCAN：一个集成癌症数据分析平台的更新。
Neoplasia. 2022 Mar;25:18-27. doi: 10.1016/j.neo.2022.01.001. Epub 2022 Jan 22.
3
Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription.
Discov Oncol. 2025 Feb 7;16(1):127. doi: 10.1007/s12672-025-01884-x.
4
Mitochondrial fatty acid synthesis is an emergent central regulator of mammalian oxidative metabolism.线粒体脂肪酸合成是哺乳动物氧化代谢的新兴核心调节因子。
Cell Metab. 2024 Jan 2;36(1):36-47. doi: 10.1016/j.cmet.2023.11.017. Epub 2023 Dec 20.
5
Inhibition of the glutamate-cysteine ligase catalytic subunit with buthionine sulfoximine enhances the cytotoxic effect of doxorubicin and cyclophosphamide in Burkitt lymphoma cells.用丁硫氨酸亚砜胺抑制谷氨酸半胱氨酸连接酶催化亚基可增强多柔比星和环磷酰胺对伯基特淋巴瘤细胞的细胞毒性作用。
J Appl Genet. 2024 Feb;65(1):95-101. doi: 10.1007/s13353-023-00797-1. Epub 2023 Nov 2.
Myc 驱动转录中非特异性和序列特异性 DNA 结合的综合需求。
EMBO J. 2021 May 17;40(10):e105464. doi: 10.15252/embj.2020105464. Epub 2021 Apr 1.
4
Global View of Candidate Therapeutic Target Genes in Hormone-Responsive Breast Cancer.激素反应性乳腺癌候选治疗靶基因的全球视野。
Int J Mol Sci. 2020 Jun 6;21(11):4068. doi: 10.3390/ijms21114068.
5
Identification of functional regulatory elements in the human genome using pooled CRISPR screens.利用 pooled CRISPR 筛选技术鉴定人类基因组中的功能调控元件。
BMC Genomics. 2020 Jan 31;21(1):107. doi: 10.1186/s12864-020-6497-0.
6
Agreement between two large pan-cancer CRISPR-Cas9 gene dependency data sets.两项大型泛癌 CRISPR-Cas9 基因依赖性数据集中的一致性。
Nat Commun. 2019 Dec 20;10(1):5817. doi: 10.1038/s41467-019-13805-y.
7
CRISPR/Cas9-based editing of a sensitive transcriptional regulatory element to achieve cell type-specific knockdown of the NEMO scaffold protein.基于 CRISPR/Cas9 的敏感转录调控元件编辑，实现 NEMO 支架蛋白的细胞类型特异性敲低。
PLoS One. 2019 Sep 25;14(9):e0222588. doi: 10.1371/journal.pone.0222588. eCollection 2019.
8
Oncogenic MYC amplifies mitotic perturbations.致癌基因 MYC 扩增有丝分裂扰动。
Open Biol. 2019 Aug 30;9(8):190136. doi: 10.1098/rsob.190136. Epub 2019 Aug 28.
9
Targeting the SLIT/ROBO pathway in tumor progression: molecular mechanisms and therapeutic perspectives.靶向SLIT/ROBO通路在肿瘤进展中的作用：分子机制与治疗前景
Ther Adv Med Oncol. 2019 Jun 6;11:1758835919855238. doi: 10.1177/1758835919855238. eCollection 2019.
10
MYC Oncogene Contributions to Release of Cell Cycle Brakes.MYC 癌基因对细胞周期刹车的释放作用。
Genes (Basel). 2019 Mar 22;10(3):244. doi: 10.3390/genes10030244.