Accession PRJCA000539
Title RNA-seq, WGBS and ChIP-seq (H3K4me2 and H3K27me3) of triple negative breast cancer stem cells and non-cancer stem cells
Relevance Medical
Data Types Epigenomics
Transcriptome or Gene expression
Raw sequence reads
Organisms Homo sapiens
Description Cancer stem cells (CSCs) refer to a group of stem cell like cells in tumor. They are thought to drive triple negative breast cancer (TNBC) recurrence because of self-renewal, high invasion and radio/chemo-therapy resistance capacities. However, how CSCs maintain their properties is still unclear. In this study, CSCs and non-CSCs were compared with respect to transcriptome, DNA methylome and the distribution of two histone modifications, H3K4me2 and H3K27me3, the latter two used as proxies for active and inactive chromatin, respectively. Transcriptome analysis result showed that eIF2, eIF4 and ephrin receptor signaling pathways were activated, whereas G1/S and G2/M cell cycle checkpoint were inhibited in CSCs, which might contribute to tumorigenicity, invasion and chemotherapy resistance of CSCs. In addition, DNA methylation analysis result indicated that genes involved in cell development process and cell-cell signaling were significantly differential methylated in CSCs. Furthermore, histone methylation analysis suggested differential enrichment of H3K4me2 and H3K27me3 might regulate cell proliferation and self-renewal process (e.g. Wnt and GnRH signaling) of CSCs. Then the integrated analysis of both transcriptome and epigenome showed eight tumor suppressors appeared to consistently down-regulate in CSCs on three levels (down-regulated expression, promoter hypermethylation and low H3K4me2 or high H3K27me3 enrichment). Based on their down-regulation, Hippo and Slit2/Robo1 signaling pathways were consequently differential regulated, which might contribute to activating proliferation, migration, invasion, tumorigenesis, metastasis and self-renewal capacity of CSCs. Finally, eIF4E, EphB4, FHL3 and MAPK13 were predicted as potential therapeutic targets of triple negative breast cancer stem cells. In all, this study offers the potential of revealing epigenetically dysregulated pathways in TNBC and of novel drug targets for urgently required treatment improvement.
Sample scope MDA-MB-231 breast cancer cell line
Release date 2017-09-08
Submitter Guochao    Li  (liguochao@big.ac.cn)
Organization Beijing Institute of Genomics, Chinese Academy of Sciences
Submission date 2017-09-04

Project Data

Resource name Description
BioSample (2) -
SAMC016542 MDA-MB-231 breast non cancer stem cells
SAMC016541 MDA-MB-231 breast cancer stem cells
GSA (1) -
CRA000465 RNA-seq, WGBS and ChIP-seq (H3K4me2 and H3K27me3) of triple negative breast cancer stem cells and non-cancer stem cells
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