, Volume 38, Issue 5, pp 3029-3035
Date: 10 Feb 2010

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

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Abstract

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: p27Kip1, p21WAF1/Cip1and TGF-β1 by in situ hybridization and immunohistochemistry respectively. p27Kip1 is one of miR-221’s proven targets. Real time qRT-PCR was used to investigate miR-221 and p27Kip1 transcripts in different clinical stages. Western blotting was used to analyze the expression levels of p27Kip1 protein in different clinical stages. In result, miR-221 and TGF-β1 are frequently up-regulated in HCC, while p27Kip1 and p21WAF1/Cip1 proteins are frequently down-regulated. Moreover, miR-221 and p27Kip1’s expression correlated with metastasis and miR-221’s expression also correlated with tumor size. Both of p21WAF1/Cip1and TGF-β1’s expression correlated with tumor differentiations. miR-221’s upregulation and p27Kip1’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 p27Kip1, a cell-cycle inhibitor. These results indicate miR-221 as a new therapeutic target in HCC.