Comprehensive analysis of differentially expressed long noncoding RNAs, miRNAs and mRNAs in breast cancer brain metastasis

Abstract

Aim: To delineate the transcriptomic landscape and potential molecular mechanisms of breast cancer brain metastasis (BCBM). Materials&methods: Whole-transcriptome sequencing was performed to identify long noncoding RNA (lncRNA), miRNA and mRNA expression profiles associated with BCBM. Results: A total of 739 differentially expressed lncRNAs, 115 differentially expressed miRNAs and 5749 differentially expressed mRNAs were identified in 231-BR cells compared with MDA-MB-231 cells. Real-time quantitative PCR results revealed the expression levels of candidate molecules were consistent with their correspondence RNA-seq data. Protein–protein interaction analysis identified some hub genes associated with BCBM, such as PTBP1, NUP98 and HYOU1. LncRNA-miRNA-mRNA network highlighted a potential mechanism of BCBM in which lncRNA FIRRE and RP11-169F17.1 sponging hsa-miR-501-5p to regulate the expression of MMS19, PTBP1 and NUP98. Conclusion: This study provides a framework for better understanding molecular mechanisms of BCBM.

Lay abstract

Breast cancer represents the second most common cause of brain metastases. Breast cancer brain metastasis (BCBM) is associated with extremely poor prognosis. Identification of molecular targets and underlying mechanisms of BCBM is a prerequisite for development of novel therapeutic agents. This study identified 739 differentially expressed lncRNAs, 115 differentially expressed miRNAs and 5749 differentially expressed mRNAs associated with BCBM. Some hub genes associated with BCBM, such as PTBP1, NUP98 and HYOU1, were also found. LncRNA-miRNA-mRNA network highlighted a potential mechanism of BCBM in which lncRNA FIRRE and RP11-169F17.1 sponging hsa-miR-501-5p to regulate the expression of MMS19, PTBP1 and NUP98. This study provides a framework for better understanding of the molecular mechanisms triggering brain metastasis, and delineating potential therapeutic targets to develop innovative treatment approaches.

Keywords::

• breast cancer brain metastasis
• expression profile
• lncRNA
• miRNA
• mRNA
• 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-2021-0152

Financial&competing interests disclosure

National Nature Science Foundation of China (grant no. 81702884), China Postdoctoral Science Foundation (grant no. 2017M612290), Nature Science Foundation of Shandong Province (grant no. ZR2016HB17), Medicine and Health Science Technology Foundation of Shandong Province (grant no. 2016WS0216 and 2015WS0381) and Science Foundation of Liaocheng People’s Hospital (grant no. LYQN201901). 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.