Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Zhanchun, Xiao, Jie, Hu, Kongzu, Wang, Gang, Li, Maoqiang, Zhang, Jidong, Cheng, Guangqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
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
_version_ 1782359741426565120
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
work_keys_str_mv AT lizhanchun fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT xiaojie fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT hukongzu fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT wanggang fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT limaoqiang fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT zhangjidong fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma
AT chengguangqi fbxw7actsasanindependentprognosticmarkerandinhibitstumorgrowthinhumanosteosarcoma