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.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (30672053), Chinese Postdoc Foundation (20070410859), The Research Initiation Fund for the Young Teachers of Medical Science of Sun Yat-Sun University(2008005) and Science and Technology Planning Project of Guangdong Province, China (2008B030301036).
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Fu, X., Wang, Q., Chen, J. et al. Clinical significance of miR-221 and its inverse correlation with p27Kip1 in hepatocellular carcinoma. Mol Biol Rep 38, 3029–3035 (2011). https://doi.org/10.1007/s11033-010-9969-5
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DOI: https://doi.org/10.1007/s11033-010-9969-5