CDC42EP3 is a key promoter involved in the development and progression of gastric cancer

Author:

Chen Wenchao123,Zhu Yuanzeng123,Zhang Wei123,Zhang Han123,Zhou Yang123,Sun Peichun123ORCID,Wu Gang123

Affiliation:

1. Department of Gastrointestinal Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan, China

2. Department of Gastrointestinal Surgery, Zhengzhou University People’s Hospital, Zhengzhou, Henan, China

3. Department of Gastrointestinal Surgery, Henan University People’s Hospital, Zhengzhou, Henan, China

Abstract

Abstract Gastric cancer (GC) is one of the most prevalent cancers and severely endangers human health. Due to the low rate of diagnosis, most patients with GC are diagnosed as advanced. CDC42 effector protein 3 (CDC42EP3) has been revealed to be involved in several types of human cancers’ development and progression. However, the function of CDC42EP3 in GC is not yet clear. CDC42EP3 expression was detected by immunohistochemistry, quantitative real-time PCR and Western blot assay in tumor tissues and cell lines of GC. CDC42EP3 knockdown cell models were constructed by lentivirus transfection. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The wound-healing assay and the transwell assay were utilized to assess the cell migration. Also, the cell apoptosis and the cell cycle were evaluated by flow cytometry. Moreover, the mechanism was investigated by Human Apoptosis Antibody Array. The in vivo experiments were conducted to verify the effects of CDC42EP3 knockdown on the tumor growth of GC. The expression level of CDC42EP3 was up-regulated in tumor tissues. High CDC42EP3 expression was positively related to more advanced tumor grade. CDC42EP3 knockdown inhibited cell proliferation and migration, promoted cell apoptosis and suppressed the tumor growth. On the other hand, it was also found that the silencing of CDC42EP3 inhibited HSP27 and IGF-1sR expression as well as promoted Caspase3, p53, TNF-α, TNF-β, TRAILR-1 and TRAILR-2 expression. CDC42EP3 was revealed to work as a tumor promoter in the development and progression of GC, which could be a promising therapeutic target for the therapy of GC.

Funder

Natural Science Foundation of Henan Province

Basic and Frontier Technology Research Project of Henan Province

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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