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.
Keywords: breast cancer brain metastasis; expression profile; lncRNA; mRNA; miRNA; therapeutic target.
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.