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Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma

icecream 添加于 2012-10-15 00:12 | 1025 次阅读 | 0 个评论

作者
Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Hiyoshi Y, Kamohara H, Baba Y, Mimori K, Baba H
摘要
BACKGROUND: F-box and WD repeat domain-containing 7 (FBXW7) is a cell cycle regulatory gene whose protein product ubiquitinates positive cell cycle regulators such as c-Myc, cyclin E, and c-Jun, thereby acting as a tumour-suppressor gene. This study focused on microRNA-223 (miR-223), which is a candidate regulator of FBXW7 mRNA. The aim of this study was to clarify the clinical significance of miR-223 and FBXW7 in oesophageal squamous cell carcinoma (ESCC) patients, and to elucidate the mechanism by which FBXW7 is regulated by miR-223. METHODS: The expression levels of miR-223 and the expression of FBXW7 protein was examined using 109 resected specimens to determine the clinicopathological significance. We also investigated the role of miR-223 in the regulation of FBXW7 expression in ESCC cell lines in an in vitro analysis. RESULTS: We found that miR-223 expression was significantly higher in cancerous tissues than in the corresponding normal tissues. There was a significant inverse relationship between the expression levels of miR-223 and FBXW7 protein. Moreover, patients with high miR-223 expression demonstrated a significantly poorer prognosis than those with low expression. On the basis of a series of gain-of-function and loss-of-function studies in vitro, we identified FBXW7 as a functional downstream target of miR-223. CONCLUSION: Our present study indicates that high expression of miR-223 had a significant adverse impact on the survival of ESCC patients through repression of the function of FBXW7.
详细资料
- 关键词: Aged; Base Sequence; Blotting, Western; Carcinoma, Squamous Cell/*enzymology/pathology; Cell Cycle Proteins/*metabolism; Cell Line, Tumor; DNA Primers; Esophageal Neoplasms/*enzymology/pathology; F-Box Proteins/*metabolism; Female; Humans; Immunohistochemistry; Male; MicroRNAs/*physiology; Middle Aged; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Ubiquitin-Protein Ligases/*metabolism
- 文献种类:期刊
- 期刊名称: British Journal of Cancer
- 期刊缩写: Br J Cancer
- 期卷页: 2012年第106卷第1期 182-188页
- 地址: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan
- ISBN: 0007-0920
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