J Cancer 2020; 11(10):2830-2844. doi:10.7150/jca.39328

Research Paper

Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells

Zucheng Xie1*, Yiwu Dang2*, Huayu Wu3, Rongquan He1, Jie Ma1, Zhigang Peng1, Minhua Rong4, Zhekun Li2, Jiapeng Yang2, Yizhao Jiang2, Gang Chen2✉, Lihua Yang1✉

1. Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.
2. Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.
3. Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, P. R. China.
4. Research Department, Affiliated Cancer Hospital, Guangxi Medical University, 71 Hedi Road, Nanning, Guangxi Zhuang Autonomous Region 530021, P. R. China.
*Equal contribution

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Citation:
Xie Z, Dang Y, Wu H, He R, Ma J, Peng Z, Rong M, Li Z, Yang J, Jiang Y, Chen G, Yang L. Effect of CELSR3 on the Cell Cycle and Apoptosis of Hepatocellular Carcinoma Cells. J Cancer 2020; 11(10):2830-2844. doi:10.7150/jca.39328. Available from http://www.jcancer.org/v11p2830.htm

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Abstract

Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) has been reported in cancers but its role and potential molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, we aimed to investigate the clinical value and molecular mechanism of CELSR3 in HCC using an in vitro experiment, a meta-analysis and bioinformatics. The in vitro experiment determined the promoting effect of CELSR3 in the proliferation, invasion, and migration of HCC cells. CELSR3 knockout causes S-phage arrest in HCC cells. CELSR3 can also inhibit the apoptosis of HCC cells. The expression of the CELSR3 gene and protein was significantly elevated in HCC. Elevated CELSR3 was correlated to the bigger tumor size, higher pathological stage, and the worse overall survival of HCC. Methylation analysis revealed that the hypomethylation of CELSR3 regulated by DNMT1, DNMT3A, and DNMT3B may be the underlying mechanism of upregulated CELSR3. Biological enrichment analysis uncovered that the cell cycle, DNA replication, and PI3K-Akt signaling pathways were important pathways regulated by CELSR3 and its co-expressed genes in HCC. Taken together, upregulated CELSR3 is an important regulator in the progression and prognosis of HCC. The hypomethylation of CELSR3 and its regulation in the cell cycle may be the potential molecular mechanism in HCC.

Keywords: hepatocellular carcinoma, CELSR3, cell cycle, apoptosis, prognosis