Hu Feihu, Liu Chenhai, Xie Fang, Lin Xiansheng, Yang Ji, Wang Chao, Huang Qiang
Department of General Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China,
Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital, Heifei, China,
Onco Targets Ther. 2018 Jul 13;11:4035-4046. doi: 10.2147/OTT.S170739. eCollection 2018.
To investigate the expression and functional role of Musashi2 (MSI2), an RNA-binding protein, in extrahepatic cholangiocarcinoma (eCCA).
We measured MSI2 expression in human specimens and cell lines using Western blot and quantitative real-time polymerase chain reaction, and we analyzed its association with clinicopathologic features in eCCA patients. Univariate and multivariate analyses were performed to identify risk factors correlated with overall survival and disease-free survival. Functional experiments were used to study the mechanisms of MSI2 in regulating eCCA cell growth, migration, and invasion.
MSI2 expression was upregulated significantly in both human specimens and cell lines, and high MSI2 expression was associated with lymph node metastasis, advanced TNM stage, and poor prognosis in eCCA patients. Additionally, MSI2 overexpression promoted eCCA cell growth, migration, and invasion, while MSI2 knockdown repressed eCCA cell migration and invasion by inhibiting epithelial-mesenchymal transition.
MSI2 is an independent prognostic factor for eCCA patients, and MSI2 downregulation inhibits eCCA cell growth and metastasis. MSI2 may be a potential therapeutic target for eCCA patients.
研究RNA结合蛋白Musashi2（MSI2）在肝外胆管癌（eCCA）中的表达及功能作用。
我们采用蛋白质免疫印迹法和定量实时聚合酶链反应检测人标本和细胞系中MSI2的表达，并分析其与eCCA患者临床病理特征的相关性。进行单因素和多因素分析以确定与总生存期和无病生存期相关的危险因素。采用功能实验研究MSI2调控eCCA细胞生长、迁移和侵袭的机制。
MSI2在人标本和细胞系中的表达均显著上调，且MSI2高表达与eCCA患者的淋巴结转移、TNM分期较晚及预后不良相关。此外，MSI2过表达促进eCCA细胞生长、迁移和侵袭，而敲低MSI2则通过抑制上皮-间质转化抑制eCCA细胞迁移和侵袭。
MSI2是eCCA患者的独立预后因素，MSI2下调抑制eCCA细胞生长和转移。MSI2可能是eCCA患者的潜在治疗靶点。
