Chen Changbao, Zhou Hua, Zhang Xiaolin, 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.
Cancer Manag Res. 2021 Jun 21;13:4911-4919. doi: 10.2147/CMAR.S313229. eCollection 2021.
The transcription factor zinc finger protein 704 (ZNF704) is implicated in tumorigenesis. However, the underlying role of ZNF704 in the pathogenesis of chondrosarcoma remains not well delineated. This study investigates the expression level, prognostic significance and potential biological function of ZNF704 in human chondrosarcoma.
The mRNA and protein levels of ZNF704 in fresh chondrosarcomas and the paired adjacent non-tumor tissues were evaluated using real-time PCR and immunoblotting, respectively. The protein expression of ZNF704 in chondrosarcoma specimens was detected by immunohistochemistry, and the associations among its expression level, clinicopathological characteristics and prognosis were further investigated. Cell viability, colony formation and apoptosis assay were determined in chondrosarcoma cells and a xenograft model with ZNF704 knockdown.
The expression levels of ZNF704 mRNA and protein in chondrosarcoma tissues were significantly higher than those in the paired adjacent non-tumor tissues and benign cartilage tumors. Clinicopathological analysis revealed that ZNF704 was expressed at higher levels in chondrosarcoma patients with higher histological grade and advanced MSTS stage. We also found that high expression of ZNF704 significantly correlated with a worse overall survival of chondrosarcoma patients. Multivariate Cox regression analysis indicated that ZNF704 was an independent prognostic marker in chondrosarcoma patients. Our in vitro studies demonstrated that knockdown of ZNF704 markedly inhibited chondrosarcoma cell viability, colony formation and induced apoptosis. In a nude mouse xenograft model, ZNF704 knockdown slowed down chondrosarcoma growth by inducing apoptosis in vivo.
These findings suggest that ZNF704 may act as a potent oncogene implicated in chondrosarcoma development, and serve as a independent prognostic marker, highlight the potential of ZNF704 as a novel biomarker and therapeutic target for chondrosarcoma.
转录因子锌指蛋白704（ZNF704）与肿瘤发生有关。然而，ZNF704在软骨肉瘤发病机制中的潜在作用仍未完全阐明。本研究调查ZNF704在人软骨肉瘤中的表达水平、预后意义及潜在生物学功能。
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ZNF704的mRNA和蛋白水平。通过免疫组织化学检测软骨肉瘤标本中ZNF704的蛋白表达，并进一步研究其表达水平、临床病理特征与预后之间的关系。在软骨肉瘤细胞和ZNF704基因敲低的异种移植模型中测定细胞活力、集落形成和凋亡检测。
软骨肉瘤组织中ZNF704的mRNA和蛋白表达水平显著高于配对的相邻非肿瘤组织和良性软骨肿瘤。临床病理分析显示，在组织学分级较高和MSTS分期较晚的软骨肉瘤患者中，ZNF704表达水平较高。我们还发现，ZNF704的高表达与软骨肉瘤患者较差的总生存期显著相关。多因素Cox回归分析表明，ZNF704是软骨肉瘤患者的独立预后标志物。我们的体外研究表明，敲低ZNF704可显著抑制软骨肉瘤细胞活力、集落形成并诱导凋亡。在裸鼠异种移植模型中，敲低ZNF704可通过在体内诱导凋亡来减缓软骨肉瘤生长。
这些发现表明，ZNF704可能作为一种有效的癌基因参与软骨肉瘤的发生发展，并作为独立的预后标志物，凸显了ZNF704作为软骨肉瘤新型生物标志物和治疗靶点的潜力。
