School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004 Ningxia Hui Autonomous Region, China; Ningxia Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, 750004 Ningxia Hui Autonomous Region, China.
Ningxia Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, 750004 Ningxia Hui Autonomous Region, China; Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, 750004 Ningxia Hui Autonomous Region, China.
Gene. 2025 Jan 15;933:148940. doi: 10.1016/j.gene.2024.148940. Epub 2024 Sep 14.
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.
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.
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/β-catenin pathway.
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.
昼夜节律基因 Brain and Muscle Arnt-like1（Bmal1）作为转录因子，在肿瘤发生和胚胎发育中发挥着关键作用。Bmal1 在各种肿瘤中显著过表达，包括神经胶质瘤。然而，Bmal1 在神经胶质瘤恶性程度中表达升高的确切机制尚不清楚。
本研究利用多个数据库，包括癌症基因组图谱（TCGA）、GTEx 和 cBioportal，分析神经胶质瘤中的 Bmal1mRNA 表达，评估其预后意义，研究转录组改变，鉴定与 Bmal1 相关的关键信号通路，并研究其与肿瘤干细胞的相互作用。此外，还进行了实验验证以确认 Bmal1 对神经胶质瘤干细胞的调节作用。
我们的分析显示 Bmal1 在不同的神经胶质瘤分级和分子亚型中表达存在差异。此外，Bmal1 显著影响几种与肿瘤相关的信号通路，特别是 Mapk、Met 和 Wnt 通路，并与干细胞密切相关。Bmal1 与神经胶质瘤干细胞标志物如 Nestin、Sox2 和 Cd133 之间存在强烈的正相关关系。实验验证证实 Bmal1 通过 Wnt/β-catenin 通路促进干细胞的扩增和肿瘤的进展。
本研究强调了 Bmal1 在神经胶质瘤发生发展中的关键调节作用。Bmal1 与神经胶质瘤干细胞之间的相互作用似乎对神经胶质瘤的发生和进展有重大影响。
