CEP192 overexpression is correlated with poor prognosis of gastric cancer and promotes gastric cancer cell proliferation by regulating PLK1/CDK1/Cyclin B1 signaling
10.12122/j.issn.1673-4254.2024.11.10
- VernacularTitle:CEP192过表达可作为胃癌患者不良预后的生物标志物并通过调控G2/M期关键蛋白的表达影响肿瘤细胞恶性增殖
- Author:
Zhen ZHANG
1
,
2
;
Hui LU
;
Xiaohua CHEN
;
Lian WANG
;
Ziliang WANG
;
Yueyue WANG
;
Sitang GE
;
Lugen ZUO
Author Information
1. 蚌埠医科大学第一附属医院 胃肠外科,安徽 蚌埠 233004
2. 蚌埠医科大学研究生院,安徽 蚌埠 233030
- Keywords:
gastric cancer;
CEP192;
poor prognosis;
proliferation;
cell cycle
- From:
Journal of Southern Medical University
2024;44(11):2137-2145
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the correlation of CEP192 expression with prognosis of gastric cancer and biological behaviors of gastric cancer cells.Methods Public databases and clinical tissue samples were used to examine CEP192 expression level in gastric cancer.Kaplan-Meier survival curves,univariate and multivariate Cox regression analyses,ROC curves and bioinformatics analyses were used to explore the risk factors affecting the 5-year postoperative survival,the correlation of CEP192 expression level with the patients'survival,and its biological role in gastric cancer development.In gastric cancer MGC-803 cells with lentivirus-mediated CEP192 interference or overexpression,cell proliferation and expressions of PLK1,CDK1 and Cyclin B1 were examined with CCK-8 assay and Western blotting.The effects of CEP192 knockdown or overexpression on tumorigenesis of MGC-803 cells was observed in nude mice,and the expressions of PLK1,CDK1 and Cyclin B1 in the xenografts were detected.Results CEP192 was highly expressed in gastric cancer and associated with poor prognosis of the patients(P<0.05).High expression of CEP192,CEA≥5 ng/mL,CA199≥37 IU/mL,T3-4 stage,and N2-3 stage were independent risk factors affecting the patients'5-year postoperative survival(P<0.05).Bioinformatics analyses suggested that CEP192 was involved in several vital biological processes and positively regulated cell cycle progression.In MGC-803 cells,CEP192 knockdown significantly inhibited cell proliferation and lowered the expression levels of PLK1,CDK1,and Cyclin B1,while its overexpression produced the opposite effects.In the nude mouse models,CEP192 knockdown resulted in lowered tumorigenic potential of MGC-803 cells and decreased protein levels of PLK1,CDK1,and Cyclin B1 in the xenografts,while CEP192 overexpression in MGC-803 cells caused the opposite changes.Conclusion CEP192 overexpression is correlated with unfavorable outcomes of gastric cancer patients and promotes gastric cell proliferation by regulating the key proteins during G2/M phase transition.
