Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial-mesenchymal transition

被引：78
作者：
He, Lu [1 ]
Zhou, Xinke [1 ]
Qu, Chen [2 ]
Hu, Lijuan [3 ]
Tang, Yunqiang [1 ]
Zhang, Qiong [4 ]
Liang, Min [1 ]
Hong, Jian [1 ]
机构：
[1] Guangzhou Med Univ, Affiliated Tumour Hosp, Dept Hepatobiliary Oncol, Guangzhou 510095, Guangdong, Peoples R China
[2] Cent South Univ, Inst Canc, Changsha, Hunan, Peoples R China
[3] Guangzhou Med Univ, Affiliated Tumour Hosp, Dept Med Oncol, Guangzhou 510095, Guangdong, Peoples R China
[4] Guangzhou Med Univ, Affiliated Tumour Hosp, Dept Pathophysiol, Guangzhou 510095, Guangdong, Peoples R China
来源：
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2014年 / 18卷 / 01期
基金：
中国国家自然科学基金;
关键词：
hepatocellular carcinoma; musashi (MSI); invasion; prognosis; biomarker; CNS STEM-CELLS; MYELOID-LEUKEMIA; BINDING; NUMB; EXPRESSION; OVEREXPRESSION; CANCER; LIVER;
D O I：
10.1111/jcmm.12158
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6% (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely detected in adjacent non-tumourous tissues and were never detected in normal hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated with poor prognosis. In addition, MSI2 up-regulation correlated with clinicopathological parameters representative of highly invasive HCC. Further study indicated that MSI2 might enhance invasion of HCC by inducing epithelial-mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the invasion of HCC cells and changed the expression pattern of EMT markers. Moreover, immunohistochemistry assays of 149 HCC tissue specimens further confirmed this correlation. Taken together, the results of our study demonstrated that MSI2 correlates with EMT and has the potential to be a new predictive biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of post-operative HCC patients.
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页码：49 / 58
页数：10
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