Zeng Yan-Ru, Han Zhao-Dong, Wang Cong, Cai Chao, Huang Ya-Qiang, Luo Hong-Wei, Liu Ze-Zhen, Zhuo Yang-Jia, Dai Qi-Shan, Zhao Hai-Bo, Liang Yu-Xiang, Zhong Wei-De
Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China.
Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, China.
BMC Urol. 2015 Aug 29;15:90. doi: 10.1186/s12894-015-0085-7.
The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. However, whether aberrant expression of NEK2 is associated with outcome of prostate cancer (PCa) patients remains to be determined.
Expression of NEK2 in human PCa cells and primary PCa tissues was assessed by quantitative RT-PCR. Expression of NEK2 in human PCa cells was depleted with siRNA. Effects of the depletion on cell proliferation, survival, and tumorigenicity were assessed both in vitro with cell cultures and in vivo with subcutaneous implantation of xenografts. In silico analyses of the online Taylor dataset were carried out to determine whether the expression level of NEK2 correlated with the clinicopathological characteristics of prostate cancer.
Compared with benign human prostatic epithelial cells and tissues, the expression of NEK2 was elevated in human PCa cells and primary PCa tissues. Depleting NEK2 expression inhibited human PCa cell proliferation in vitro and xenograft growth in vivo. Expression level of NEK2 in PCa positively correlated with the Gleason score and pathologic stage of the patient.
The results suggest that overexpression of NEK2 has the potential to serve as a biomarker for PCa prognosis. Further validation with large sample pool is warrant.
NIMA相关激酶2(NEK2)是一种丝氨酸/苏氨酸激酶,参与有丝分裂期间中心体复制和纺锤体组装的调控。这些过程的失调会导致染色体不稳定和非整倍体,这是许多实体瘤的标志性变化。然而,NEK2的异常表达是否与前列腺癌(PCa)患者的预后相关仍有待确定。
通过定量逆转录聚合酶链反应(qRT-PCR)评估NEK2在人PCa细胞和原发性PCa组织中的表达。用小干扰RNA(siRNA)降低人PCa细胞中NEK2的表达。通过细胞培养在体外以及通过皮下植入异种移植物在体内评估这种降低对细胞增殖、存活和致瘤性的影响。对在线泰勒数据集进行计算机分析,以确定NEK2的表达水平是否与前列腺癌的临床病理特征相关。
与良性人前列腺上皮细胞和组织相比,NEK2在人PCa细胞和原发性PCa组织中的表达升高。降低NEK2表达可抑制体外人PCa细胞增殖和体内异种移植物生长。PCa中NEK2的表达水平与患者的 Gleason评分和病理分期呈正相关。
结果表明,NEK2的过表达有可能作为PCa预后的生物标志物。需要用大样本库进行进一步验证。