Transcriptomic and Epigenetic Analysis of Breast Cancer Stem Cells

Abstract

Aim: Cancer stem cells (CSCs) drive triple-negative breast cancer recurrence via their properties of self-renewal, invasiveness and radio/chemotherapy resistance. This study examined how CSCs might sustain these properties. Materials & methods: Transcriptomes, DNA methylomes and histone modifications were compared between CSCs and non CSCs. Results: Transcriptome analysis revealed several pathways that were activated in CSCs, whereas cell cycle regulation pathways were inhibited. Cell development and signaling genes were differentially methylated, with histone methylation analysis suggesting distinct H3K4me2 and H3K27me3 enrichment profiles. An integrated analysis revealed several tumor suppressor genes downregulated in CSCs. Conclusion: Differential activation of various signaling pathways and genes contributes to the tumor-promoting properties of CSCs. Therapeutic targets identified in the analysis may contribute to improving treatment options for patients.

Keywords::

• breast cancer stem cells
• DNA methylation
• epigenome
• histone modification
• H3K27me3
• H3K4me2
• multiple omics analysis
• transcriptome

Author’s contributions

Y Sun conceived this study. G Li, D Wang and H Yu facilitated the experimental design. D Wang, W Ma, Z Liu, C Yang, F Du, X Han, S Chang, H Yu, Z Zhang and Z Zhao performed the basic biological experiments. G Li and D Wang performed bioinformatics data analysis and interpretation with the help of Y Zhang and J Wang. G Li, D Wang, K An and X Han wrote the paper with the assistance of other authors. All authors revised the manuscript.

Financial & competing interests disclosure

This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDA01040407), National Natural Science Foundation of China (grant no. 81702796), the National Basic Research Program of China (973 Program, grant no. 2013CB911001), and Precision Medicine Research Program of the Chinese Academy of Sciences (grant no. KJZD-EW-L14). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDA01040407), National Natural Science Foundation of China (grant no. 81702796), the National Basic Research Program of China (973 Program, grant no. 2013CB911001), and Precision Medicine Research Program of the Chinese Academy of Sciences (grant no. KJZD-EW-L14). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.