Li Zhiwei, Jin Hui, Mao Guozhang, Wu Liuguang, Guo Qingwei
Department of Thoracic Surgery, Zhoukou Central Hospital, China.
Department of Thoracic Surgery, Zhoukou Central Hospital, China.
Exp Cell Res. 2017 Dec 1;361(1):170-177. doi: 10.1016/j.yexcr.2017.10.016. Epub 2017 Oct 18.
Msi2 has been widely reported to be upregulated and strongly associated with fast progress and poor prognosis in many cancers. However, the expression and role of Msi2 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we found that Msi2 was upregulated in ESCC clinical samples, and was significantly associated with tumor size, differentiation status, and lymph node metastasis in ESCC patients. Multivariate Cox regression analysis showed that Msi2 was an independent predictor for disease-free survival (DFS) and overall survival (OS). Moreover, knockdown of Msi2 impaired ESCC cell proliferation, epithelial-mesenchymal transition (EMT) and migration, while overexpression of Msi2 promoted ESCC cell proliferation, EMT and migration in vitro. Animal experiments also confirmed that Msi2 promoted ESCC cell proliferation in vivo. Mechanistically, Msi2 promoted ESCC cell proliferation, EMT and migration via regulation of the Wnt/β-catenin and Hedgehog (Hh) signaling pathways. Taken together, our study suggested that Msi2 could serve as a candidate for diagnosis and prognosis and as a potential therapeutic target in ESCC.
已有广泛报道称，Msi2在许多癌症中表达上调，并与快速进展和不良预后密切相关。然而，Msi2在食管鳞状细胞癌（ESCC）中的表达及作用仍不清楚。在本研究中，我们发现Msi2在ESCC临床样本中表达上调，且与ESCC患者的肿瘤大小、分化状态及淋巴结转移显著相关。多因素Cox回归分析显示，Msi2是无病生存期（DFS）和总生存期（OS）的独立预测因子。此外，敲低Msi2会损害ESCC细胞增殖、上皮-间质转化（EMT）和迁移，而在体外过表达Msi2则会促进ESCC细胞增殖、EMT和迁移。动物实验也证实，Msi2在体内可促进ESCC细胞增殖。机制上，Msi2通过调控Wnt/β-连环蛋白和Hedgehog（Hh）信号通路促进ESCC细胞增殖、EMT和迁移。综上所述，我们的研究表明，Msi2可作为ESCC诊断和预后的候选指标以及潜在的治疗靶点。
