High expression of TMEM40 is associated with the malignant behavior and tumorigenesis in bladder cancer.
High expression of TMEM40 is associated with the malignant behavior and tumorigenesis in bladder cancer.
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TMEM40的高表达与膀胱癌的恶性行为和肿瘤发生有关
DOI：
10.1186/s12967-017-1377-3
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发表时间：
2018-01-19
影响因子：
7.4
通讯作者：
Zhou JY
中科院分区：
文献类型：
--
作者：
Zhang ZF;Zhang HR;Zhang QY;Lai SY;Feng YZ;Zhou Y;Zheng SR;Shi R;Zhou JY
膀胱癌（Bladder cancer，BCa）是泌尿系统最常见的恶性肿瘤之一。既往研究表明TMEM 40表达水平与膀胱癌的组织学分级、临床分期和pT状态等临床病理参数显著相关。方法采用实时荧光定量RT-PCR（qRT-PCR）和Western blot（WB）方法检测TMEM 40在BCa组织、配对非癌组织和细胞系中的表达水平。通过CCK-8、伤口愈合、流式细胞术、transwell和EdU等实验，研究TMEM 40对细胞增殖、细胞周期和凋亡、迁移和侵袭的影响。此外，使用异种皮下植入模型在体内评价肿瘤生长。所有统计分析均采用SPSS20.0软件进行。所有实验数据从三个独立的实验进行了分析，学生的t检验和结果表示为平均值±标准偏差。ResultsIn这项研究中，我们确定了TMEM 40的作用在膀胱癌的肿瘤发生，并发现它是上调膀胱癌组织和细胞系，与他们的正常同行。结果表明，TMEM 40表达的有效沉默抑制细胞增殖，阻断G1至S细胞周期转换，并抑制人膀胱5637和EJ细胞系的细胞迁移和侵袭。一致地，体内数据显示TMEM 40沉默可显著降低肿瘤生长。结论TMEM 40可能是一种潜在的癌基因，通过p53信号通路在BCa的增殖和凋亡中发挥重要作用，因此TMEM 40有可能成为BCa的一个新的候选生物标志物和潜在的治疗靶点。
BackgroundBladder cancer (BCa) is one of the most common cancers in the urinary system among the world. Previous studies suggested that TMEM40 expression level was significantly associated with clinicopathological parameters including histological grade, clinical stage and pT status of bladder cancer. However, the molecular mechanism of TMEM40 in BCa remains poorly understood.MethodsReal-time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell lines. A series of experiments, including CCK-8, wound healing, flow cytometry, transwell and EdU assays were performed to assess the effects of TMEM40 on cell proliferation, cell cycle and apoptosis, migration and invasion. In addition, tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model. All statistical analyses were executed by using the SPSS 20.0 software. All experimental data from three independent experiments were analyzed by Student’sttest and results were expressed as mean ± standard deviation.ResultsIn this study, we identified the role of TMEM40 in the tumorigenesis of bladder cancer and found that it was upregulated in bladder cancer tissues and cell lines, compared with their normal counterparts. The results demonstrated that effective silence of TMEM40 expression suppressed cell proliferation, blocked G1-to-S cell cycle transition, and inhibited cell migration and invasion in human bladder 5637 and EJ cell lines. Consistently, in vivo data showed that TMEM40 silencing could dramatically decreased tumor growth. Further study revealed that TMEM40 knockdown resulted in accumulation of p53 and p21 protein and decrease of c-MYC and cyclin D1 protein.ConclusionThese data suggest that TMEM40 represents a potential oncogene, which exert a crucial role in the proliferation and apoptosis via the p53 signaling pathway in BCa, thus probably serve as a novel candidate biomarker and a potential therapeutic target for patients with BCa.
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