Identification of potential target genes of breast cancer in response to Chidamide treatment.
Identification of potential target genes of breast cancer in response to Chidamide treatment.
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DOI：
10.3389/fmolb.2022.999582
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
Chidamide是一种新的化学结构的HDACi样药物，已被证明可以抑制乳腺癌，但其具体机制尚未完全阐明。本论文选取ER阳性乳腺癌MCF-7细胞，利用RNA-seq技术分析西达胺作用后乳腺癌细胞的基因表达差异，以确定西达胺抗乳腺癌作用的药物靶点，为开发乳腺癌治疗新药奠定基础。结果显示，MCF-7 CHID组与对照组相比，有320个基因表达上调，222个基因表达下调; Gene Ontology功能富集分析显示，大部分基因富集到生物学过程中。随后，使用Cytoscape插件CytoHubba根据高分确定了10个用于Chidamide治疗乳腺癌的中心基因：TP 53、JUN、CAD、ACLY、IL-6、过氧化物酶体增殖物激活受体γ、THBS 1、CXCL 8、IMPDH 2和YARS。最后，结合基因表达谱交互分析数据库和Kaplan Meier作图法比较这10个枢纽基因TP 53、ACLY、PPARG和JUN的表达和存活分析，发现它们是与西达胺显著相关的潜在候选基因，用于乳腺癌治疗。其中，TP 53可能是西达胺克服乳腺癌多药耐药的潜在靶基因。因此，我们通过生物信息学分析确定了四个与Chidamide治疗乳腺癌相关的基因，并阐明TP 53可能是Chidamide克服乳腺癌多药耐药的潜在靶基因。本研究为西达米特在分子水平上治疗乳腺癌及联合用药奠定了坚实的实验和理论基础。
Chidamide, a new chemically structured HDACi-like drug, has been shown to inhibit breast cancer, but its specific mechanism has not been fully elucidated. In this paper, we selected ER-positive breast cancer MCF-7 cells and used RNA-seq technique to analyze the gene expression differences of Chidamide-treated breast cancer cells to identify the drug targets of Chidamide’s anti-breast cancer effect and to lay the foundation for the development of new drugs for breast cancer treatment. The results showed that the MCF-7 CHID group expressed 320 up-regulated genes and 222 down-regulated genes compared to the control group; Gene Ontology functional enrichment analysis showed that most genes were enriched to biological processes. Subsequently, 10 hub genes for Chidamide treatment of breast cancer were identified based on high scores using CytoHubba, a plug-in for Cytoscape: TP53, JUN, CAD, ACLY, IL-6, peroxisome proliferator-activated receptor gamma, THBS1, CXCL8, IMPDH2, and YARS. Finally, a combination of the Gene Expression Profiling Interactive Analysis database and Kaplan Meier mapper to compare the expression and survival analysis of these 10 hub genes, TP53, ACLY, PPARG, and JUN were found to be potential candidate genes significantly associated with Chidamide for breast cancer treatment. Among them, TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. Therefore, we identified four genes central to the treatment of breast cancer with Chidamide by bioinformatics analysis, and clarified that TP53 may be a potential target gene for Chidamide to overcome multi-drug resistance in breast cancer. This study lays a solid experimental and theoretical foundation for the treatment of breast cancer at the molecular level with Chidamide and for the combination of Chidamide.
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影响因子：
4.6
作者：
Ujihira T;Ikeda K;Suzuki T;Yamaga R;Sato W;Horie-Inoue K;Shigekawa T;Osaki A;Saeki T;Okamoto K;Takeda S;Inoue S
通讯作者：
Inoue S
影响因子：
4.6
作者：
He J;Wang K;Zheng N;Qiu Y;Xie G;Su M;Jia W;Li H
通讯作者：
Li H
影响因子：
29
作者：
Corbet, Cyril;Pinto, Adan;Feron, Olivier
通讯作者：
Feron, Olivier
DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
3.2
作者：
Hong, Bo;van den Heuvel, A. Pieter J.;El-Deiry, Wafik S.
通讯作者：
El-Deiry, Wafik S.