Association of FBXW11 levels with tumor development and prognosis in chondrosarcoma

Abstract

INTRODUCTION: The E3 ubiquitin ligase FBXW11 exerts an oncogenic or tumor suppressive function in a cellular context-dependent manner. However, the clinical significance and biological role of FBXW11 in chondrosarcoma have not been clearly characterized. This study focuses on the expression profile, prognostic value and biological function of FBXW11 in chondrosarcoma. METHODS: FBXW11 expression was analyzed by qRT-PCR and Western blot in six cases of chondrosarcoma specimens and the matched adjacent non-tumor tissues. The expression profile and prognostic value of FBXW11 were investigated in sixty-three cases of chondrosarcoma patients. Cell viability, colony formation, migration, invasion and apoptosis assays were further detected in SW1353 chondrosarcoma cells with restored FBXW11 expression. RESULTS: Downregulation of FBXW11 was remarkably detected in human chondrosarcoma specimens compared with the corresponding non-tumor tissues and benign cartilage tumors. Downregulated FBXW11 expression significantly correlated with high-grade chondrosarcoma and poor prognosis. Furthermore, FBXW11 was identified as an independent prognostic factor for the overall survival of chondrosarcoma patients. Restored expression of FBXW11 significantly suppressed chondrosarcoma cell growth and induced apoptosis. CONCLUSIONS: These findings establish that FBXW11 was markedly downregulated and recognized as an independent prognostic factor for patients with chondrosarcoma, and restored FBXW11 expression can suppress chondrosarcoma growth and induce apoptosis, highlighting a novel biological marker and potential therapeutic target against chondrosarcoma.

Epigenetic Regulation of Neuroinflammation in Alzheimer’s Disease

“…Cao et al disclosed that the UPP contributes to receptor-interacting serine/threonine kinase 1 (RIPK1) degradation mediated by optineurin (OPTN) in microglial cells to inhibit the proinflammatory pathways of NF-κB and, thus, suppresses neuroinflammation [ 138 ]. F-box and WD-40-domain protein 11 (FBXW11) is a component of the SCF (Skp1-Cul1-F-box) E3 ubiquitin ligase complex [ 139 , 140 ]. A study conducted by Sun et al showed FBXW11, a component of the SCF E3 ubiquitin ligase complex, was overexpressed in Aβ-stimulated microglia cells and the hippocampus of AD mice, and it enabled the activation of the ASK1/MAPKs/NF-κB inflammatory signaling pathway, thereby contributing to inflammation-induced AD pathology.…”

Beta-Transducin Repeats-Containing Proteins as an Anticancer Target

“…A high level of expression of β-TrCP2 has been reported in human cancer cell lines and primary breast tumors [104]. On the contrary, the downregulation of β-TrCP2 has been reported in clinical chondrosarcoma samples [105]. In addition, the recovery of β-TrCP2 suppresses chondrosarcoma cell growth and induces apoptosis.…”