Chen Changbao, Zhou Hua, Liu Zhongjun, Ma Xinlong
Department of Spinal Surgery, Tianjin Hospital, Tianjin, 300211, People's Republic of China.
Department of Orthopaedic Surgery, Peking University Third Hospital, Beijing, 100191, People's Republic of China.
Onco Targets Ther. 2021 Jun 1;14:3545-3553. doi: 10.2147/OTT.S310164. eCollection 2021.
The transcription factor zinc finger protein 395 (ZNF395) is involved in several cellular responses and tumorigenesis. However, the potential role and clinical significance of ZNF395 in chondrosarcoma are not well investigated. This study determines the expression profile, prognostic value and biological function of ZNF395 in human chondrosarcoma.
The mRNA and protein expressions of ZNF395 in fresh chondrosarcomas and the matched adjacent non-tumor tissues were assessed using real-time PCR and immunoblotting, respectively. The protein expression of ZNF395 in chondrosarcoma specimens was evaluated by immunohistochemistry, and the relationships among its protein level, clinicopathological parameters and prognosis were further detected. Cell viability, colony formation, migration, invasion and apoptosis assay were evaluated in chondrosarcoma cells with depletion of ZNF395.
The mRNA and protein expressions of ZNF395 in chondrosarcoma tissues were significantly higher than those in the matched adjacent non-tumor tissues and benign cartilage tumors. Clinical analysis displayed that ZNF395 was expressed at higher levels in chondrosarcoma patients with higher histological grade and advanced MSTS stage. Furthermore, we demonstrated that high expression of ZNF395 correlated with a worse overall survival of chondrosarcoma patients. Multivariate Cox regression analysis indicated that ZNF395 was an independent prognostic marker in chondrosarcoma patients. Functional studies revealed that depletion of ZNF395 markedly inhibited cell viability, colony formation, migration and invasion, and promoted apoptosis in chondrosarcoma.
These findings suggest that dysregulation of ZNF395 contributes to chondrosarcoma development, and ZNF395 may act as a potent oncogene and serve as a independently prognostic factor, highlight the potential of ZNF395 as a novel biomarker and therapeutic target for chondrosarcoma.
转录因子锌指蛋白395（ZNF395）参与多种细胞反应和肿瘤发生。然而，ZNF395在软骨肉瘤中的潜在作用和临床意义尚未得到充分研究。本研究确定ZNF395在人软骨肉瘤中的表达谱、预后价值和生物学功能。
分别采用实时PCR和免疫印迹法评估新鲜软骨肉瘤及配对的相邻非肿瘤组织中ZNF395的mRNA和蛋白表达。通过免疫组织化学评估软骨肉瘤标本中ZNF395的蛋白表达，并进一步检测其蛋白水平、临床病理参数与预后之间的关系。对ZNF395缺失的软骨肉瘤细胞进行细胞活力、集落形成、迁移、侵袭和凋亡检测。
软骨肉瘤组织中ZNF395的mRNA和蛋白表达显著高于配对的相邻非肿瘤组织和良性软骨肿瘤。临床分析显示，在组织学分级较高和MSTS分期较晚的软骨肉瘤患者中，ZNF395表达水平较高。此外，我们证明ZNF395的高表达与软骨肉瘤患者较差的总生存期相关。多因素Cox回归分析表明，ZNF395是软骨肉瘤患者的独立预后标志物。功能研究表明，ZNF395缺失显著抑制软骨肉瘤细胞的活力、集落形成、迁移和侵袭，并促进其凋亡。
这些发现表明ZNF395失调促进软骨肉瘤发展，ZNF395可能作为一种有效的癌基因并作为独立的预后因素，突出了ZNF395作为软骨肉瘤新型生物标志物和治疗靶点的潜力。
