Study on the mechanism of CDCA8 promoting the occurrence of prostate cancer by regulating proliferation

doi:10.11958/20212744

Abstract

Abstract:

Objective To explore the expression and mechanism of cell division cycle associated protein 8 (CDCA8) in the occurrence of prostate cancer (PCa). Methods The difference of CDCA8 mRNA expression levels between normal prostate tissue and PCa tissue was analyzed by bioinformatics method. The disease-free survival (DFS) associated with CDCA8 expression in PCa patients was analyzed using RNA sequencing data from cancer Genome Atlas (TCGA) database. Immunohistochemical method was used to detect the expression of CDCA8 in 56 pairs of PCa tissues and adjacent tissues after radical prostatectomy. Patients were divided into the CDCA8 high expression group (n=31) and the CDCA8 low expression group (n=25) according to staining results. The potential correlation between clinical characteristics and CDCA8 expression level was further analyzed. The CDCA8 gene was silenced by siRNA, and the expression level of CDCA8 mRNA was detected by qPCR. The proliferation of PCa cells was detected by clonal formation assay, and the changes of CDCA8, Ki67, proliferating cell nuclear antigen (PCNA) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway proteins were detected by Western blot assay. Results In TCGA database, CDCA8 mRNA level was significantly higher in PCa tissues than that in normal tissues, and patients with high expression of CDCA8 mRNA had a worse prognosis (P<0.01). The staining index of expression level of CDCA8 protein was significantly higher in PCa tissue than that in para-cancer tissue, and the expression level was positively correlated with total prostate-specific antigen (tPSA), Gleason score, T stage and surgical margin (P<0.01). The proportion of patients with tPSA≥10 μg/L, T3 stage and positive postoperative resection margin was significantly higher in the high CDCA8 expression group than that in the low CDCA8 expression group (P<0.05). After CDCA8 gene was silenced, the proliferation of PCa cells was decreased, and the protein expression levels of Ki67, PCNA, p-PI3K and p-AKT were down-regulated (P<0.01). Conclusion CDCA8 promotes the occurrence of prostate cancer by regulating proliferation, and its mechanism may be related to PI3K/AKT signaling pathway.

Key words: prostatic neoplasms, cell proliferation, proliferating cell nuclear antigen, cell cycle proteins, CDCA8, PI3K/AKT signaling pathway

CLC Number:

R737.25

Figures/Tables 12

References 21

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组别	n	CDCA8 蛋白	年龄（岁）	tPSA（μg/L）		Gleason评分		T分期		N分期		术后切缘
组别	n	CDCA8 蛋白	年龄（岁）	<10	≥10	<7	≥7	T1~T2	T3	N0	N1	阴性	阳性
低表达组	25	1.92±0.28	68.84±6.23	9（36.0）	16（64.0）	5（20.0）	20（80.0）	19（76.0）	6（24.0）	24（96.0）	1（4.0）	19（76.0）	6（24.0）
高表达组	31	3.48±0.51	68.58±6.26	3（9.7）	28（90.3）	1（3.2）	30（96.8）	15（48.4）	16（51.6）	24（77.4）	7（22.6）	9（29.0）	22（71.0）
t或χ²		14.653^＊＊	0.154	5.695^＊＊		2.506		4.424^＊		2.532		12.212^＊＊

组别	n	CDCA8 蛋白	年龄（岁）	tPSA（μg/L）		Gleason评分		T分期		N分期		术后切缘
组别	n	CDCA8 蛋白	年龄（岁）	<10	≥10	<7	≥7	T1~T2	T3	N0	N1	阴性	阳性
低表达组	25	1.92±0.28	68.84±6.23	9（36.0）	16（64.0）	5（20.0）	20（80.0）	19（76.0）	6（24.0）	24（96.0）	1（4.0）	19（76.0）	6（24.0）
高表达组	31	3.48±0.51	68.58±6.26	3（9.7）	28（90.3）	1（3.2）	30（96.8）	15（48.4）	16（51.6）	24（77.4）	7（22.6）	9（29.0）	22（71.0）
t或χ²		14.653^＊＊	0.154	5.695^＊＊		2.506		4.424^＊		2.532		12.212^＊＊

组别	CDCA8 mRNA		CDCA8蛋白
组别	PC3	DU145	PC3	DU145
Si-NC组	1.12±0.06	1.00±0.05	1.20±0.01	1.05±0.01
Si-CDCA8组	0.15±0.01	0.15±0.01	0.56±0.01	0.30±0.01
t	27.129^＊＊	28.121^＊＊	74.929^＊＊	147.377^＊＊

组别	CDCA8 mRNA		CDCA8蛋白
组别	PC3	DU145	PC3	DU145
Si-NC组	1.12±0.06	1.00±0.05	1.20±0.01	1.05±0.01
Si-CDCA8组	0.15±0.01	0.15±0.01	0.56±0.01	0.30±0.01
t	27.129^＊＊	28.121^＊＊	74.929^＊＊	147.377^＊＊

组别	PC3	DU145
Si-NC组	316.67±6.43	522.67±4.04
Si-CDCA8组	160.67±14.01	348.33±7.37
t	17.527^＊＊	35.920^＊＊