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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

CDK-associated Cullin 1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Human Glioblastoma

Author(s): Xiaohua Zhang, Tianying Zhang, Xiaojuan Han, Zhongying Qiu, Jianghong Cheng, Xingchun Gao and Xingchun Gou*

Volume 21, Issue 10, 2021

Published on: 02 June, 2021

Page: [870 - 880] Pages: 11

DOI: 10.2174/1568009621666210602164225

Price: $65

Abstract

Background: 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.

Objective: This study aims to explore the role of CACUL1 in the pathogenesis of human glioma.

Methods: 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.

Results: 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.

Conclusion: CACUL1 can promote cell proliferation and suppress apoptosis of glioma cells and might serve as a potential oncogene for gliomas.

Keywords: CACUL1, glioma, proliferation, apoptosis, CDK2, cell cycle.

Graphical Abstract
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