研究动态
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通过对整合的ChIP-seq和转录组数据的荟萃分析揭示了雌激素受体α在乳腺癌中受影响的基因组区域。

Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer.

发表日期:2023 Sep 15
作者: Zeynab Piryaei, Zahra Salehi, Esmaeil Ebrahimie, Mansour Ebrahimi, Kaveh Kavousi
来源: BIOMEDICINE & PHARMACOTHERAPY

摘要:

乳腺癌患者中最大的一个群体是雌激素受体阳性(ER+)类型。雌激素受体作为转录因子,能够触发细胞增殖和分化。因此,调查ER-DNA相互作用的基因组区域可以帮助识别直接受ER调控的基因,并理解ER在癌症进展中的作用机制。本研究采用一个工作流程对ER+细胞系受到10 nM和100 nM E2刺激的ChIP-seq数据进行了荟萃分析。所有公开可用的数据集都使用相同的平台重新分析。然后,消除已知和未知的批次效应。最后,进行荟萃分析,以获得与车辆(对照组)相比,雌激素处理的MCF7细胞系中的荟萃差异结合位点。还将荟萃分析结果与T47D细胞系的结果进行比较,以获得更精确的结果。还进行了富集分析,以找到两个细胞系之间共有的荟萃差异结合位点和相关基因的功能重要性。 值得注意的是,在荟萃分析中,发现了POU5F1B、ZNF662、ZNF442、KIN、ZNF410和SGSM2转录因子,但在个体研究中没有发现。荟萃差异结合位点的富集结果提供了之前在乳腺癌中未报告的途径的候选。通过富集分析还预测出了PCGF2、HNF1B和ZBED6转录因子。此外,比较ChIP-seq和RNA-seq数据的荟萃分析结果表明,ER影响的许多转录因子都被上调。 对雌激素处理的MCF7细胞系的ChIP-seq数据进行荟萃分析,发现了以前未报道的ER新结合位点。此外,荟萃差异结合位点及其相关基因的富集分析还揭示了乳腺癌发展中涉及的新术语和途径,这些应该在未来的体外和体内研究中进行检验。 © 2023. BioMed Central Ltd., part of Springer Nature.
The largest group of patients with breast cancer are estrogen receptor-positive (ER+) type. The estrogen receptor acts as a transcription factor and triggers cell proliferation and differentiation. Hence, investigating ER-DNA interaction genomic regions can help identify genes directly regulated by ER and understand the mechanism of ER action in cancer progression.In the present study, we employed a workflow to do a meta-analysis of ChIP-seq data of ER+ cell lines stimulated with 10 nM and 100 nM of E2. All publicly available data sets were re-analyzed with the same platform. Then, the known and unknown batch effects were removed. Finally, the meta-analysis was performed to obtain meta-differentially bound sites in estrogen-treated MCF7 cell lines compared to vehicles (as control). Also, the meta-analysis results were compared with the results of T47D cell lines for more precision. Enrichment analyses were also employed to find the functional importance of common meta-differentially bound sites and associated genes among both cell lines.Remarkably, POU5F1B, ZNF662, ZNF442, KIN, ZNF410, and SGSM2 transcription factors were recognized in the meta-analysis but not in individual studies. Enrichment of the meta-differentially bound sites resulted in the candidacy of pathways not previously reported in breast cancer. PCGF2, HNF1B, and ZBED6 transcription factors were also predicted through the enrichment analysis of associated genes. In addition, comparing the meta-analysis results of both ChIP-seq and RNA-seq data showed that many transcription factors affected by ER were up-regulated.The meta-analysis of ChIP-seq data of estrogen-treated MCF7 cell line leads to the identification of new binding sites of ER that have not been previously reported. Also, enrichment of the meta-differentially bound sites and their associated genes revealed new terms and pathways involved in the development of breast cancer which should be examined in future in vitro and in vivo studies.© 2023. BioMed Central Ltd., part of Springer Nature.