大规模功能缺失扰动揭示了乳腺癌的综合表观遗传调控网络。

IF 5.6 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Yumei Wang, Haiyan Wang, Wei Shao, Yuhui Chen, Yu Gui, Chao Hu, Xiaohong Yi, Lijun Huang, Shasha Li, Dong Wang
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引用次数: 0

摘要

目的:表观遗传异常通过调控基因表达在乳腺癌中起着至关重要的作用;然而,大约400种表观遗传调控因子在乳腺癌中错综复杂的相互关系和关键作用仍然难以捉摸。破译乳腺癌细胞中全面的表观遗传调控网络对确定主表观遗传调控因子和潜在的治疗靶点非常重要:方法:我们采用基于高通量测序的高通量筛选(HTS2)技术,有效检测了敲除400个表观遗传调控因子后2986个基因的表达变化。然后,利用生物信息学分析工具对得到的基因表达特征进行分析,以研究乳腺癌的表观遗传调控:结果:利用这些基因表达特征,我们将表观遗传调控因子分为五个不同的群组,每个群组都具有特定的功能。我们发现 BAZ2B 和 SETMAR 以及 CLOCK 和 CBX3 在功能上具有相似性。此外,我们还观察到 CLOCK 在下游基因调控中的功能与 HDAC8 相反。值得注意的是,我们根据基因表达特征构建了表观遗传调控网络,发现了8个不同的模块,并确定了乳腺癌中的10个表观遗传主调控因子:我们的研究破译了数百个表观遗传调控因子之间的广泛调控。结论:我们的研究破译了数百个表观遗传调控因子之间的广泛调控,并确定了 10 个主表观遗传调控因子,为乳腺癌治疗提供了有前景的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer.

Objective: Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression; however, the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive. It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.

Methods: We employed high-throughput sequencing-based high-throughput screening (HTS2) to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators. Then, bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.

Results: Utilizing these gene expression signatures, we classified the epigenetic regulators into five distinct clusters, each characterized by specific functions. We discovered functional similarities between BAZ2B and SETMAR, as well as CLOCK and CBX3. Moreover, we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation. Notably, we constructed an epigenetic regulatory network based on the gene expression signatures, which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.

Conclusions: Our work deciphered the extensive regulation among hundreds of epigenetic regulators. The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

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来源期刊
Cancer Biology & Medicine
Cancer Biology & Medicine Medicine-Oncology
CiteScore
9.80
自引率
3.60%
发文量
1143
审稿时长
12 weeks
期刊介绍: Cancer Biology & Medicine (ISSN 2095-3941) is a peer-reviewed open-access journal of Chinese Anti-cancer Association (CACA), which is the leading professional society of oncology in China. The journal quarterly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China.
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