Cancer Gene Ther. 2026 Aug 10. doi: 10.1038/s41417-026-01065-0. Online ahead of print.
ABSTRACT
Breast cancer (BRCA) development is tightly linked to metabolic dysregulation, with enhanced aerobic glycolysis standing out as a key hallmark, and competing endogenous RNA (ceRNA) mechanisms have emerged as critical epigenetic regulators of tumor metabolic pathways-this study thus aimed to explore glycolytic regulation through ceRNA networks in BRCA, with the goal of identifying potential prognostic biomarkers and mechanistic targets. To achieve this, we integrated comprehensive bioinformatics analyses of The Cancer Genome Atlas (TCGA) dataset with experimental validation to identify PCAT7 as a functionally relevant long non-coding RNA (lncRNA), complemented by functional assays including cell proliferation tests, glucose consumption measurements, and lactate production assays, as well as molecular interaction verification using luciferase reporter assays and RNA immunoprecipitation (RIP). Our results showed that PCAT7 is overexpressed in BRCA tissues and correlates with poor patient prognosis; mechanistically, PCAT7 acts as a molecular sponge for miR-204-5p, alleviating its inhibitory effect on RUNX2 and thereby regulating key glycolytic regulators including GLUT1 and PKM2, while silencing PCAT7 suppresses tumor cell proliferation, invasion, migration, and glycolytic activity in vitro. Collectively, this study uncovers a novel ceRNA network involving PCAT7/miR-204-5p/RUNX2 that drives glycolytic metabolism in BRCA, advancing our understanding of epigenetic regulation in cancer metabolism and highlighting PCAT7 as a potential prognostic biomarker for BRCA patients, with future in vivo studies needed to further validate the therapeutic potential of targeting this axis. Created in https://BioRender.com .
PMID:42576052 | DOI:10.1038/s41417-026-01065-0
