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, Koshi Mimori, H. Baba

Research output: Contribution to journalArticle

97 Citations (Scopus)

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

Fingerprint

Ligases
Ubiquitin
MicroRNAs
Esophageal Squamous Cell Carcinoma
cdc Genes
Cyclin E
Proteins
Regulator Genes
Tumor Suppressor Genes
Cell Cycle
Cell Line
Messenger RNA
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kurashige, J., Watanabe, M., Iwatsuki, M., Kinoshita, K., Saito, S., Hiyoshi, Y., ... 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

Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. / Kurashige, J.; Watanabe, M.; Iwatsuki, M.; Kinoshita, K.; Saito, S.; Hiyoshi, Y.; Kamohara, H.; Baba, Y.; Mimori, Koshi; Baba, H.

In: British journal of cancer, Vol. 106, No. 1, 03.01.2012, p. 182-188.

Research output: Contribution to journalArticle

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, vol. 106, no. 1, pp. 182-188. https://doi.org/10.1038/bjc.2011.509
Kurashige, J. ; Watanabe, M. ; Iwatsuki, M. ; Kinoshita, K. ; Saito, S. ; Hiyoshi, Y. ; Kamohara, H. ; Baba, Y. ; Mimori, Koshi ; Baba, H. / Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. In: British journal of cancer. 2012 ; Vol. 106, No. 1. pp. 182-188.
@article{2d03a3c1eab74bc1b609247a4e1d38de,
title = "Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma",
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.",
author = "J. Kurashige and M. Watanabe and M. Iwatsuki and K. Kinoshita and S. Saito and Y. Hiyoshi and H. Kamohara and Y. Baba and Koshi Mimori and H. Baba",
year = "2012",
month = "1",
day = "3",
doi = "10.1038/bjc.2011.509",
language = "English",
volume = "106",
pages = "182--188",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma

AU - Kurashige, J.

AU - Watanabe, M.

AU - Iwatsuki, M.

AU - Kinoshita, K.

AU - Saito, S.

AU - Hiyoshi, Y.

AU - Kamohara, H.

AU - Baba, Y.

AU - Mimori, Koshi

AU - Baba, H.

PY - 2012/1/3

Y1 - 2012/1/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84855346886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855346886&partnerID=8YFLogxK

U2 - 10.1038/bjc.2011.509

DO - 10.1038/bjc.2011.509

M3 - Article

C2 - 22108521

AN - SCOPUS:84855346886

VL - 106

SP - 182

EP - 188

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -