Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma

被引:65
作者
Fu, Xinhui [2 ,3 ]
Wang, Qian [1 ]
Chen, Jingsong [1 ]
Huang, Xiaohui [2 ]
Chen, Xilin [1 ]
Cao, Liangqi [1 ]
Tan, Haoxiang [1 ]
Li, Wen [2 ]
Zhang, Longjuan [2 ]
Bi, Jiong [2 ]
Su, Qiao [2 ]
Chen, Lianzhou [2 ]
机构
[1] Sun Yat Sen Zhongshan Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Zhongshan Univ, Lab Surg, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Zhongshan Univ, Affiliated Hosp 6, Inst Gastrointestinal Dis, Guangzhou 510655, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
HCC; In situ hybridization; miR-221; p27(Kip1); MICRORNA EXPRESSION;
D O I
10.1007/s11033-010-9969-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
The aim of the present study is to explore possible role of miR-221 in the pathogenesis of HCC. Matched HCC and adjacent non-cancerous samples were assayed for the expression of miR-221 and three G1/S transition inhibitors: p27(Kip1), p21(WAF1/Cip1)and TGF-beta 1 by in situ hybridization and immunohistochemistry respectively. p27(Kip1) is one of miR-221's proven targets. Real time qRT-PCR was used to investigate miR-221 and p27(Kip1) transcripts in different clinical stages. Western blotting was used to analyze the expression levels of p27(Kip1) protein in different clinical stages. In result, miR-221 and TGF-beta 1 are frequently up-regulated in HCC, while p27(Kip1) and p21(WAF1/Cip1) proteins are frequently down-regulated. Moreover, miR-221 and p27(Kip1)'s expression correlated with metastasis and miR-221's expression also correlated with tumor size. Both of p21(WAF1/Cip1)and TGF-beta 1's expression correlated with tumor differentiations. miR-221's upregulation and p27(Kip1)'s downregulation were significantly associated with tumor stages and metastasis. In conclusion, miR-221 is important in tumorigenesis of HCC, possibly by specifically down-regulating p27(Kip1), a cell-cycle inhibitor. These results indicate miR-221 as a new therapeutic target in HCC.
引用
收藏
页码:3029 / 3035
页数:7
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