The H19/miR-760/BST2 regulatory axis sustains breast cancer tumorigenesis and metastasis.

Abstract

The long noncoding RNA H19 has been widely attested as a promoter of breast cancer by favoring proliferation, migration, invasion, and tumor growth. In this study, we attempted to decipher molecular mechanisms underlying oncogenic activities of H19. Transcriptomic analyses revealed that H19 overexpression correlates with increased BST2 expression at both transcriptional and protein levels in breast cancer cell lines. Functional assays demonstrated that BST2 overexpression mimics H19 oncogenic effects by enhancing tumor cell aggressiveness in vitro and tumor growth in vivo. Interestingly, we also observed a reciprocal regulation, where BST2 expression modulates H19 levels, suggesting a cross-regulatory mechanism. Further mechanistic studies identified miR-760 as a key post-transcriptional regulator orchestrating this interplay. Using luciferase reporter assays and miRNA modulation strategies, we found that miR-760 directly targets both H19 and BST2, thereby regulating their expression in a coordinated manner. Our findings uncover a novel H19/miR-760/BST2 regulatory axis that enhances breast cancer progression and suggest that this axis could be studied to identify potential targets for therapeutic intervention.