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

KURASHIGE, J ; WATANABE, M ; LWATSUKI, M ; KINOSHITA, K ; SAITO, S ; HIYOSHI, Y ; KAMOHARA, H ; BABA, Y ; MIMORI, K ; BABA, H

British journal of cancer, 2012-01, Vol.106 (1), p.182-188 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma
Autor: KURASHIGE, J ; WATANABE, M ; LWATSUKI, M ; KINOSHITA, K ; SAITO, S ; HIYOSHI, Y ; KAMOHARA, H ; BABA, Y ; MIMORI, K ; BABA, H
Assuntos: Aged ; Base Sequence ; Biological and medical sciences ; Blotting, Western ; Cancer research ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - pathology ; Cell cycle ; Cell Cycle Proteins - metabolism ; Cell Line, Tumor ; DNA Primers ; Esophageal Neoplasms - enzymology ; Esophageal Neoplasms - pathology ; Esophagus ; F-Box Proteins - metabolism ; F-Box-WD Repeat-Containing Protein 7 ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Immunohistochemistry ; Male ; Medical prognosis ; Medical research ; Medical sciences ; MicroRNAs ; MicroRNAs - physiology ; Middle Aged ; Molecular Diagnostics ; Prognosis ; Proteins ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Surgery ; Tumors ; Ubiquitin-Protein Ligases - metabolism
É parte de: British journal of cancer, 2012-01, Vol.106 (1), p.182-188
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Descrição: 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. 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. 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. 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.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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

KURASHIGE, J ; WATANABE, M ; LWATSUKI, M ; KINOSHITA, K ; SAITO, S ; HIYOSHI, Y ; KAMOHARA, H ; BABA, Y ; MIMORI, K ; BABA, H

Basingstoke: Nature Publishing Group

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