Circular RNA dynamics in breast-to-brain metastatic cascade

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Breast-to-brain metastases (BTB mets) are aggressive cancers with poor outcomes.
• Metastatic colonization involves complex transcriptomic reprogramming, including non-coding RNAs.
• Circular RNAs (circRNAs) are emerging regulators in cancer, but their role in BTB mets is unclear.

Purpose of the Study:

• To systematically profile circRNA expression in primary breast tumors and metastatic sites.
• To identify site-specific circRNA patterns associated with BTB mets.
• To explore the regulatory mechanisms of circRNAs in brain metastasis.

Main Methods:

• Comprehensive circRNA profiling across primary tumors and metastatic sites.
• Differential expression analysis to identify BTB mets-specific circRNAs.
• Functional analysis of circRNA-microRNA interactions and pathway enrichment.

Main Results:

• CircRNAs exhibit highly site-specific expression patterns during breast cancer metastasis.
• Most differentially expressed circRNAs were independent of their host genes.
• 42 circRNAs were consistently deregulated in BTB mets, enriched in brain-related pathways.
• circRNA landscapes remained stable under stemness or differentiation conditions.
• Breast circScope, an open-access resource, was developed for circRNA data exploration.

Conclusions:

• CircRNAs represent a significant layer of post-transcriptomic regulation in metastatic breast cancer.
• Site-specific circRNA expression patterns are associated with metastatic progression to the brain.
• CircRNAs are integral to the regulatory landscape of BTB mets, offering insights into brain tropism.