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

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/Cip1and TGF-??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-??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/Cip1and TGF-??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.