Zhang Xiaohua, Zhang Tianying, Han Xiaojuan, Qiu Zhongying, Cheng Jianghong, Gao Xingchun, Gou Xingchun
Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi’an 710021, China
School of Basic Medical Sciences & Shaanxi Key Laboratory of Brain Disorders, Xi’an Medical University, Xi’an, 710021, P.R. China
Curr Cancer Drug Targets. 2021;21(10):870-880. doi: 10.2174/1568009621666210602164225.
Glioma is the most common intracranial primary tumour of adult humans, and its pathological mechanism and molecular characteristics are still under investigation. CDK-associated cullin 1 (CACUL1) has been shown to regulate colorectal carcinoma, lung cancer, and gastric cancer development.
This study aims to explore the role of CACUL1 in the pathogenesis of human glioma.
CACUL1 levels in human glioma tissue microarrays were detected by immunohistochemistry analysis. Two glioblastoma cell lines, namely, U87 and U251, were transfected with CACUL1 siRNA, and cell proliferation, cell cycle, cell apoptosis, and regulating molecules, including cyclinE1, cyclinA2, CDK2, p21, Bcl2, and Bax were assessed by CCK8, flow cytometry, and Western blot.
CACUL1 expression in glioma tissue was significantly higher than that in normal brain tissue. CACUL1 knockdown impeded cell proliferation, induced cell apoptosis, and caused G1/S transition arrest in glioblastoma cells. The cell cycle-related proteins CDK2, cyclinE1, and cyclinA2 were dramatically decreased in the CACUL1 siRNA group compared to the non-targeting siRNA group in both U87 and U251 cells, while the CDK inhibitory protein p21 was increased in U87 cells. Additionally, the Bcl-2/Bax ratio was significantly decreased.
CACUL1 can promote cell proliferation and suppress apoptosis of glioma cells and might serve as a potential oncogene for gliomas.
胶质瘤是成人中最常见的颅内原发性肿瘤，其病理机制和分子特征仍在研究中。已表明细胞周期蛋白依赖性激酶相关的cullin 1（CACUL1）可调节结直肠癌、肺癌和胃癌的发展。
本研究旨在探讨CACUL1在人类胶质瘤发病机制中的作用。
通过免疫组织化学分析检测人胶质瘤组织芯片中CACUL1的水平。用CACUL1 siRNA转染两种胶质母细胞瘤细胞系，即U87和U251，并通过CCK8、流式细胞术和蛋白质免疫印迹法评估细胞增殖、细胞周期、细胞凋亡以及调节分子，包括细胞周期蛋白E1、细胞周期蛋白A2、细胞周期蛋白依赖性激酶2（CDK2）、p21、Bcl-2和Bax。
胶质瘤组织中CACUL1的表达明显高于正常脑组织。敲低CACUL1可抑制胶质母细胞瘤细胞的增殖，诱导细胞凋亡，并导致G1/S期转换停滞。与非靶向siRNA组相比，在U87和U251细胞中，CACUL1 siRNA组的细胞周期相关蛋白CDK2、细胞周期蛋白E1和细胞周期蛋白A2显著降低，而U87细胞中CDK抑制蛋白p21增加。此外，Bcl-2/Bax比值显著降低。
CACUL1可促进胶质瘤细胞的增殖并抑制其凋亡，可能是胶质瘤的潜在癌基因。
