Zhang Zhongmian, Liu Ping, Wang Jian, Gong Tianxiao, Zhang Fang, Ma Jun, Han Na
Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University School of Medicine, Central Laboratory, No. 2, Jingba Rd, Zhengzhou, 450000, Henan, China.
Med Oncol. 2015 May;32(5):149. doi: 10.1007/s12032-015-0609-8. Epub 2015 Apr 2.
The oncogenic role of ubiquitin-conjugating enzyme E2C (UBE2C) had been identified in some types of human tumors, while the clinical and biological role of UBE2C in non-small cell lung cancer (NSCLC) is still elusive. Here, we have determined the specific role of UBE2C in NSCLC. Western blot and qRT-PCR were used for detecting the mRNA level and protein level of UBE2C in NSCLC samples and cell lines, respectively. Lentivirus product was used to conduct loss of function assay. qRT-PCR array was employed to detect potential downstream genes regulated by UBE2C. As the result, UBE2C mRNA level was approximately threefold overexpression in NSCLC tissues compared with normal tissues, while a sharp change was detected at protein level. Overexpression of UBE2C in lung cancer samples was correlated with advanced pathological stage. UBE2C regulated cell growth in an apoptosis-dependent way. PCR Array analysis revealed that UBE2C regulated the expression of genes associated with tumor growth, apoptosis, and angiogenesis. Furthermore, UBE2C could regulate phospho-ERK1/2 level but not STAT3, YAP, or AKT pathway, which was accompanied with the classic function of ERK pathway in cell growth and apoptosis. In conclusion, our results indicated UBE2C might be a novel therapeutic target in NSCLC.
泛素结合酶E2C(UBE2C)的致癌作用已在某些类型的人类肿瘤中得到证实,而UBE2C在非小细胞肺癌(NSCLC)中的临床和生物学作用仍不清楚。在此,我们确定了UBE2C在NSCLC中的具体作用。分别使用蛋白质印迹法和qRT-PCR检测NSCLC样本和细胞系中UBE2C的mRNA水平和蛋白质水平。利用慢病毒产物进行功能缺失实验。采用qRT-PCR芯片检测受UBE2C调控的潜在下游基因。结果显示,与正常组织相比,NSCLC组织中UBE2C的mRNA水平约为三倍过表达,而蛋白质水平则有明显变化。肺癌样本中UBE2C的过表达与晚期病理分期相关。UBE2C以细胞凋亡依赖的方式调节细胞生长。PCR芯片分析表明,UBE2C调节与肿瘤生长、细胞凋亡和血管生成相关的基因表达。此外,UBE2C可调节磷酸化ERK1/2水平,但不影响STAT3、YAP或AKT信号通路,这与ERK信号通路在细胞生长和凋亡中的经典功能一致。总之,我们的结果表明UBE2C可能是NSCLC的一个新的治疗靶点。