Chen Zhuangfei, Xiao Kanghua, Zhang Hao, Liu Cundong, Yang Jiankun, Liang Haitao, Lin Zhijun, Qin Zike, Chen Mingkun, Ye Yunlin
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Transl Cancer Res. 2020 Apr;9(4):2588-2598. doi: 10.21037/tcr.2020.02.67.
MAP kinase-interacting kinase 1 (MNK1) has been reported to be over-expressed in several cancers, however, its expression level and biological function in bladder cancer (BCa) remains unclear.
Besides analyzing human publicly available dataset, we used quantitative real-time PCR, western blotting and immunohistochemistry to evaluate the expression of MNK1 in BCa and the adjacent normal bladder epithelial tissues. In vitro and in vivo proliferation assays including cell counting kit-8 and xenograft assay were carried out to explore the role of MNK1 in BCa. Chi-square test and Cox proportional hazards regression model were performed to describe MNK1's clinical significance in BCa patients.
Compared to normal bladder epithelia, MNK1 was down-regulated in the clinical tumor specimens and cell lines of BCa both at mRNA and protein level. MNK1 expression was found significantly associated with advanced T status and poor overall survival (OS) of BCa patients who had received radical cystectomy and was an independent prognostic biomarker for OS. Biological function assays demonstrated that MNK1 could impair the proliferation capacities of BCa cell lines both and .
Unlike other cancers, MNK1 is low-expressed in BCa tissues and could inhibit the proliferation ability of BCa cells, which suggests that MNK1 might play as a tumor suppressor in BCa.
有报道称丝裂原活化蛋白激酶相互作用激酶1(MNK1)在多种癌症中过表达,然而,其在膀胱癌(BCa)中的表达水平和生物学功能仍不清楚。
除了分析公开可用的人类数据集外,我们还使用定量实时PCR、蛋白质印迹和免疫组织化学来评估MNK1在BCa和相邻正常膀胱上皮组织中的表达。进行了包括细胞计数试剂盒-8和异种移植试验在内的体外和体内增殖试验,以探讨MNK1在BCa中的作用。采用卡方检验和Cox比例风险回归模型来描述MNK1在BCa患者中的临床意义。
与正常膀胱上皮相比,MNK1在BCa的临床肿瘤标本和细胞系中的mRNA和蛋白质水平均下调。发现MNK1表达与接受根治性膀胱切除术的BCa患者的晚期T分期和较差的总生存期(OS)显著相关,并且是OS的独立预后生物标志物。生物学功能试验表明,MNK1在体内和体外均可损害BCa细胞系的增殖能力。
与其他癌症不同,MNK1在BCa组织中低表达,并且可以抑制BCa细胞的增殖能力,这表明MNK1可能在BCa中发挥肿瘤抑制作用。