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敲低CDCA8可抑制膀胱癌细胞的增殖并增强其凋亡。

Knockdown of CDCA8 inhibits the proliferation and enhances the apoptosis of bladder cancer cells.

作者信息

Gao Xin, Wen Xiaohong, He Haowei, Zheng Linlin, Yang Yibo, Yang Jinlian, Liu Haifang, Zhou Xiguo, Yang Changshun, Chen Yinyi, Chen Mei, Zhang Shufang

机构信息

Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan, China.

Clinical Laboratory, The First People's Hospital of Huaihua of University of South China, Huaihua, China.

出版信息

PeerJ. 2020 Apr 28;8:e9078. doi: 10.7717/peerj.9078. eCollection 2020.

Abstract

Bladder cancer is a tumour of the urinary system with high mortality, and there is also a great lack of therapeutic targets in the clinic. Cell division cycle associated 8 (CDCA8), an important component of the vertebrate chromosomal passenger complex, is highly expressed in various tumours and promotes tumour development. However, the role of CDCA8 in bladder cancer is not fully understood. This study aimed to reveal the function of CDCA8 in bladder cancer by determining the relationship between CDCA8 expression and proliferation, metastasis and apoptosis of bladder cancer cells. Firstly, we studied the mRNA expression of CDCA8 through the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and analysed the correlation between CDCA8 expression and prognosis of patients with bladder cancer. We also verified CDCA8 expression in bladder cancer tissues by immunohistochemistry. In addition, CDCA8 expression was inhibited in bladder cancer T24 and 5637 cells, and the effects of CDCA8 on the proliferation, migration and invasion of bladder cancer cell lines were investigated using cell counting kit-8, colony formation, cell cycle, apoptosis, wound healing and Transwell invasion assays. Results showed that CDCA8 was highly expressed in bladder cancer compared with normal tissues, and the high CDCA8 expression was significantly correlated with the poor prognosis of patients. Inhibiting CDCA8 expression inhibited the proliferation, migration and invasion of T24 and 5637 cells and induced the apoptosis of bladder cancer cells. CDCA8 was involved in the regulation of the growth cycle of bladder cancer cells. Bioinformatics-based mechanism analysis revealed that high CDCA8 expression may affect the cell cycle and P53 signalling pathways. In conclusion, our results suggest that CDCA8 is highly expressed in bladder cancer and can promote tumour development. Hence, CDCA8 may serve as an effective therapeutic target for treatment of bladder cancer.

摘要

膀胱癌是一种死亡率很高的泌尿系统肿瘤,临床上也非常缺乏治疗靶点。细胞分裂周期相关蛋白8(CDCA8)是脊椎动物染色体乘客复合体的重要组成部分,在各种肿瘤中高表达并促进肿瘤发展。然而,CDCA8在膀胱癌中的作用尚未完全明确。本研究旨在通过确定CDCA8表达与膀胱癌细胞增殖、转移和凋亡之间的关系,揭示CDCA8在膀胱癌中的功能。首先,我们通过基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库研究了CDCA8的mRNA表达,并分析了CDCA8表达与膀胱癌患者预后的相关性。我们还通过免疫组织化学验证了膀胱癌组织中CDCA8的表达。此外,在膀胱癌细胞T24和5637中抑制CDCA8表达,并使用细胞计数试剂盒-8、集落形成、细胞周期、凋亡、伤口愈合和Transwell侵袭实验研究CDCA8对膀胱癌细胞系增殖、迁移和侵袭的影响。结果显示,与正常组织相比,CDCA8在膀胱癌中高表达,且CDCA8高表达与患者的不良预后显著相关。抑制CDCA8表达可抑制T24和5637细胞的增殖、迁移和侵袭,并诱导膀胱癌细胞凋亡。CDCA8参与调控膀胱癌细胞的生长周期。基于生物信息学的机制分析表明,CDCA8高表达可能影响细胞周期和P53信号通路。总之,我们的结果表明,CDCA8在膀胱癌中高表达并可促进肿瘤发展。因此,CDCA8可能作为治疗膀胱癌的有效治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa2f/7194097/dfc0c9466626/peerj-08-9078-g001.jpg

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