FBXW7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma.

Zhanchun Li,Jie Xiao,Maoqiang Li,Gang Wang,Guangqi Cheng,Kongzu Hu,Jidong Zhang

doi:10.3390/ijms16022294

Abstract

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.

Highlights

Osteosarcoma (OS) is the most common primary malignant cancer in bone [1]
To determine the expression of F-box and WD repeat domain-containing 7 (FBXW7) in OS specimens, we evaluated the levels of FBXW7 expression in 68 collected OS tissues and 20 collected normal bone tissues using immunoblotting
Quantitative analysis indicated that the level of FBXW7 mRNA in OS tissues was lower compared with that in normal bone tissues (p < 0.05, Figure 1B)

Summary

Introduction

Osteosarcoma (OS) is the most common primary malignant cancer in bone [1]. Previous studies showed that the incidence of OS is correlated with patient age [2]. The annual incidence of OS is 0.017%. In children under 10 years old, and 0.082% in children 10 to 19 years old [2]. Emerging evidence has shown that major advances in diagnosis and treatment have improved the outlook for OS patients, but satisfactory curative effects have not yet been achieved. It is important to explore new biomarkers for predicting the prognosis and improving the outcome of OS patients. FBXW7 (F-box and WD repeat domain-containing 7), called hCDC4, is a well-characterized

Results

Discussion

Conclusion