Gu Xuefeng, Mao Yuan, Shi Chuanbing, Ye Wei, Hou Ning, Xu Li, Chen Yan, Zhao Wei
Medical School, Southeast University, Nanjing, People's Republic of China.
Department of Liver Disease, The Second Hospital of Nanjing, Medical School, Southeast University, Nanjing, People's Republic of China.
Onco Targets Ther. 2019 Sep 24;12:7843-7855. doi: 10.2147/OTT.S213164. eCollection 2019.
Although MAGEC2 was first cloned from a human hepatocellular carcinoma (HCC) cDNA library by serum screening, the detailed attributes of MAGEC2 in HCC have rarely been elucidated.
In this study, The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were consulted to analyse the expression of MAGEC2 mRNA in liver cancer. Immunohistochemistry (IHC) analysis was performed to detect MAGEC2 expression in HCC, and the relationship between MAGEC2 expression and the clinicopathological characteristics of HCC patients was evaluated. Then, we employed the short hairpin (sh)RNA-mediated knockdown of MAGEC2 in HCC cell lines to explore the function of MAGEC2 in HCC development. Finally, the expression of epithelial-mesenchymal transition (EMT) markers in HCC xenografts and clinical samples was investigated.
The results showed a remarkably higher level of MAGEC2 expression in HCC tissues than in noncancerous tissues, and MAGEC2 expression could be used as an independent prognostic factor for overall survival in HCC. Moreover, sh-MAGEC2 inhibited a series of HCC malignant behaviours both in vitro and in vivo. Finally, decreased MAGEC2 expression and low levels of EMT markers were detected in sh-MAGEC2 xenografts, while increased MAGEC2 expression and high levels of EMT markers were observed in invasive and metastatic HCC samples.
Taken together, our data imply that MAGEC2 is a novel prognostic marker for HCC and that MAGEC2 significantly promotes HCC tumourigenesis by inducing EMT. Targeting MAGEC2 may provide a promising therapeutic strategy for HCC treatment.
尽管MAGEC2最初是通过血清筛选从人肝细胞癌（HCC）cDNA文库中克隆出来的，但MAGEC2在HCC中的详细特性鲜有阐明。
在本研究中，查阅了癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）以分析MAGEC2 mRNA在肝癌中的表达。进行免疫组织化学（IHC）分析以检测MAGEC2在HCC中的表达，并评估MAGEC2表达与HCC患者临床病理特征之间的关系。然后，我们采用短发夹（sh）RNA介导的方法在HCC细胞系中敲低MAGEC2，以探索MAGEC2在HCC发生发展中的功能。最后，研究了HCC异种移植瘤和临床样本中上皮-间质转化（EMT）标志物的表达。
结果显示，HCC组织中MAGEC2的表达水平显著高于非癌组织，且MAGEC2表达可作为HCC总体生存的独立预后因素。此外，sh-MAGEC2在体外和体内均抑制了一系列HCC的恶性行为。最后，在sh-MAGEC2异种移植瘤中检测到MAGEC2表达降低和EMT标志物水平较低，而在侵袭性和转移性HCC样本中观察到MAGEC2表达增加和EMT标志物水平较高。
综上所述，我们的数据表明MAGEC2是HCC的一种新型预后标志物，且MAGEC2通过诱导EMT显著促进HCC的肿瘤发生。靶向MAGEC2可能为HCC治疗提供一种有前景的治疗策略。
