Bmal1 regulates the stemness and tumorigenesis of gliomas with the Wnt/ß-catenin signaling pathway.

ABSTRACT

BACKGROUND: The circadian rhythm gene Brain and Muscle Arnt-like1 (Bmal1) acts as a transcription factor and plays a crucial role in oncogenesis and embryonic development. Bmal1 is notably overexpressed in various tumors, including glioma. However, the precise mechanisms underlying the elevated Bmal1 expression in glioma malignancy remain unclear. METHODS: This study employed multiple databases, including The Cancer Genome Atlas (TCGA), GTEx, and cBioportal, to analyze Bmal1 mRNA expression in gliomas, evaluate its prognostic significance, investigate transcriptome alterations, identify key signaling pathways associated with Bmal1, and examine its interaction with tumor stem cells. Additionally, experimental validation was performed to confirm Bmal1's regulatory effects on glioma stem cells. RESULTS: Our analysis revealed differential Bmal1 expression across glioma grades and molecular subtypes. Moreover, Bmal1 significantly influences several tumor-related signaling pathways, notably the Mapk, Met, and Wnt pathways, and is actively involved with stem cells. A strong positive correlation was observed between Bmal1 and glioma stem cell markers, such as Nestin, Sox2, and Cd133. Experimental validation confirmed that Bmal1 promotes stem cell expansion and tumor progression via the Wnt/ß-catenin pathway. CONCLUSION: This study underscores the critical regulatory function of Bmal1 in glioma development. The interaction between Bmal1 and glioma stem cells appears to significantly impact glioma initiation and progression.