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/Cip1)and TGF-β1 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-β1 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-β1'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.
Fu
Xinhui
X
Laboratory of Surgery, The First Affiliated Hospital, Sun Yat-Sen (Zhongshan) University, Guangzhou, 510080 Guangdong, People's Republic of China.
Wang
Qian
Q
Chen
Jingsong
J
Huang
Xiaohui
X
Chen
Xilin
X
Cao
Liangqi
L
Tan
Haoxiang
H
Li
Wen
W
Zhang
Longjuan
L
Bi
Jiong
J
Su
Qiao
Q
Chen
Lianzhou
L
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data
D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; C525709:MIR221, human