Circular RNA Profile of Breast Cancer Brain Metastasis: Identification of Potential Biomarkers and Therapeutic Targets

Abstract

Aim: To explore the circular RNA (circRNA) profile of breast cancer brain metastasis (BCBM). Materials & methods: RNA-seq was performed to identify the circRNA expression profile of brain metastatic breast cancer cell line 231-BR, in comparison with its parental nonspecific metastatic cell line MDA-MB-231. Results: A total of 215 upregulated and 191 downregulated circRNAs were identified. The expression levels of ten randomly selected majorly altered circRNAs were re-examined by real-time quantitative PCR and agarose gel electrophoresis, and the following alterations were verified: upregulation of hsa_circ_0001944, hsa_circ_0001481, hsa_circ_0000646, hsa_circ_0001006 and hsa_circ_0000732, and downregulation of hsa_circ_0001910, hsa_circ_0008285 and hsa_circ_0000002. CircRNA/miRNA analysis revealed that hsa_circ_0001944 may be involved in BCBM through sponging up miR-509 and interfering with its binding to the downstream targets. Conclusion: This study provides a leading and fundamental circRNA profile of BCBM.

Keywords::

• biomarker
• breast cancer brain metastasis
• circular RNA
• expression profile
• therapeutic target

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2018-0090

Acknowledgements

The authors would like to thank PS Steeg (National Cancer Institute, Bethesda, MD, USA) for the 231-BR and MDA-MB-231 cell lines.

Author’s contributions

W Liu, M An and J Zhang conceived and designed the study. B Fu, A Zhang, M Li, L Pan and W Tang performed experiments and analyzed data. B Fu and A Zhang wrote the main manuscript text and prepared all of the tables and figures. All authors reviewed the manuscript before submission. All the authors approved the final version of the manuscript.

Financial & competing interests disclosure

This study was funded by Nature Science Foundation of Shandong Province (grant number ZR2016HB17), National Nature Science Foundation of China (grant number 81702884), China Postdoctoral Science Foundation (grant number 2017M612290) and Medicine and Health Science Technology Foundation of Shandong Province (grant number 2015WS0381 and 2016WS0216). 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 study was approved by the ethics committee of Liaocheng People’s Hospital (permit number: 2017022). All procedures performed in studies involving human or animal experimental investigations were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki. For investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was funded by Nature Science Foundation of Shandong Province (grant number ZR2016HB17), National Nature Science Foundation of China (grant number 81702884), China Postdoctoral Science Foundation (grant number 2017M612290) and Medicine and Health Science Technology Foundation of Shandong Province (grant number 2015WS0381 and 2016WS0216). 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.