ArticleCellular oncology (Dordrecht, Netherlands)2026
CircBARD1 suppresses tumor progression driven by H3K18 lactylation-CCNA2 axis in human bladder cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBladder cancer (BCa) represents the fourth most prevalent malignancy worldwide, characterized by unfavorable clinical outcomes. The functional significance and molecular mechanisms underlying circular RNAs in BCa pathogenesis require further investigation. This study reveals that circBARD1 suppresses histone lactylation-driven tumor progression by modulating ENO1 protein stability in bladder cancer.
methodsFunctional characterization of circBARD1 was performed through gain-of-function experiments in T24 and TCCSUP cell lines. RNA immunoprecipitation (RIP) and immunoprecipitation assays were employed to investigate circBARD1-ENO1 interactions. CUT&Tag and chromatin immunoprecipitation (ChIP) assays were conducted to examine H3K18 lactylation-mediated transcriptional regulation of CCNA2.
resultsCircBARD1 expression was significantly downregulated in bladder cancer tissues. Ectopic expression of circBARD1 inhibited malignant proliferation and migration capacities in BCa cell lines. Furthermore, circBARD1 demonstrated negative regulation of glycolytic flux and intracellular lactate accumulation. Mechanistic studies revealed that circBARD1 physically interacts with ENO1 protein, facilitating its ubiquitination-mediated proteasomal degradation mediated by FBXW7. This circBARD1/ENO1 regulatory axis attenuates tumor progression through suppression of H3K18 lactylation and subsequent downregulation of CCNA2 transcription.
conclusionsOur findings establish that circBARD1 functions as a tumor suppressor in bladder cancer by promoting ENO1 ubiquitination and degradation, thereby inhibiting histone lactylation-mediated oncogenesis. This study provides new insights into therapeutic targets for clinical management of bladder cancer.
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