Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma
Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma
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DOI：
10.1007/s11033-010-9969-5
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发表时间：
2011-06-01
影响因子：
2.8
通讯作者：
Chen, Lianzhou
中科院分区：
文献类型：
--
作者：
Fu, Xinhui;Wang, Qian;Chen, Lianzhou
本研究的目的是探讨miR-221在HCC发病机制中的可能作用。通过原位杂交和免疫组织化学分别检测匹配的HCC和邻近的非癌样本中miR-221和三种G1/S过渡抑制剂：p27(Kip1), p21（WAF1/Cip1）和tgf - β 1的表达。p27（Kip1）是miR-221已证实的靶点之一。Real - time qRT-PCR检测miR-221和p27（Kip1）转录本在不同临床阶段的表达情况。Western blotting分析p27（Kip1）蛋白在不同临床分期的表达水平。结果，miR-221和tgf - β 1在HCC中经常上调，而p27（Kip1）和p21（WAF1/Cip1）蛋白经常下调。此外，miR-221和p27（Kip1）的表达与转移相关，miR-221的表达也与肿瘤大小相关。p21（WAF1/Cip1）和tgf - β 1的表达均与肿瘤分化相关。miR-221的上调和p27（Kip1）的下调与肿瘤分期和转移显著相关。总之，miR-221在HCC的肿瘤发生中很重要，可能是通过特异性下调p27(Kip1)，一种细胞周期抑制剂。这些结果表明miR-221是HCC的一个新的治疗靶点。
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.