Department of Spinal Surgery, Tianjin Hospital, Tianjin, China.
Department of Orthopaedic Surgery, Peking University Third Hospital, Beijing, China.
Cancer Biomark. 2022;35(4):429-437. doi: 10.3233/CBM-210426.
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.
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.
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.
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.
E3 泛素连接酶 FBXW11 在细胞环境依赖的方式下发挥致癌或抑癌功能。然而,FBXW11 在软骨肉瘤中的临床意义和生物学作用尚未得到明确的描述。本研究重点研究了 FBXW11 在软骨肉瘤中的表达谱、预后价值和生物学功能。
通过 qRT-PCR 和 Western blot 分析 6 例软骨肉瘤标本及其配对的非肿瘤组织中 FBXW11 的表达。通过 qRT-PCR 分析 63 例软骨肉瘤患者的 FBXW11 表达谱和预后价值。进一步在恢复 FBXW11 表达的 SW1353 软骨肉瘤细胞中检测细胞活力、集落形成、迁移、侵袭和凋亡。
与相应的非肿瘤组织和良性软骨肿瘤相比,人软骨肉瘤标本中 FBXW11 的表达明显下调。下调的 FBXW11 表达与高级别软骨肉瘤和不良预后显著相关。此外,FBXW11 被鉴定为软骨肉瘤患者总生存期的独立预后因素。恢复 FBXW11 的表达显著抑制软骨肉瘤细胞生长并诱导凋亡。
这些发现表明,FBXW11 明显下调,并被认为是软骨肉瘤患者的独立预后因素,恢复 FBXW11 的表达可以抑制软骨肉瘤的生长并诱导凋亡,强调了针对软骨肉瘤的新的生物学标志物和潜在的治疗靶点。