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FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma
F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were signifi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346837/ https://www.ncbi.nlm.nih.gov/pubmed/25622249 http://dx.doi.org/10.3390/ijms16022294 |
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author | Li, Zhanchun Xiao, Jie Hu, Kongzu Wang, Gang Li, Maoqiang Zhang, Jidong Cheng, Guangqi |
author_facet | Li, Zhanchun Xiao, Jie Hu, Kongzu Wang, Gang Li, Maoqiang Zhang, Jidong Cheng, Guangqi |
author_sort | Li, Zhanchun |
collection | PubMed |
description | F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. |
format | Online Article Text |
id | pubmed-4346837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43468372015-04-03 FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma Li, Zhanchun Xiao, Jie Hu, Kongzu Wang, Gang Li, Maoqiang Zhang, Jidong Cheng, Guangqi Int J Mol Sci Article F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. MDPI 2015-01-22 /pmc/articles/PMC4346837/ /pubmed/25622249 http://dx.doi.org/10.3390/ijms16022294 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Zhanchun Xiao, Jie Hu, Kongzu Wang, Gang Li, Maoqiang Zhang, Jidong Cheng, Guangqi FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title | FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title_full | FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title_fullStr | FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title_full_unstemmed | FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title_short | FBXW7 Acts as an Independent Prognostic Marker and Inhibits Tumor Growth in Human Osteosarcoma |
title_sort | fbxw7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346837/ https://www.ncbi.nlm.nih.gov/pubmed/25622249 http://dx.doi.org/10.3390/ijms16022294 |
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