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

J. Kurashige, M. Watanabe, M. Iwatsuki, K. Kinoshita, S. Saito, Y. Hiyoshi, H. Kamohara, Y. Baba, K. Mimori, H. Baba

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Abstract

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.

Original languageEnglish
Pages (from-to)182-188
Number of pages7
JournalBritish journal of cancer
Volume106
Issue number1
DOIs
Publication statusPublished - Jan 3 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kurashige, J., Watanabe, M., Iwatsuki, M., Kinoshita, K., Saito, S., Hiyoshi, Y., Kamohara, H., Baba, Y., Mimori, K., & Baba, H. (2012). Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. British journal of cancer, 106(1), 182-188. https://doi.org/10.1038/bjc.2011.509