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锌指蛋白560(ZNF560)在骨肉瘤中作为一种新的致癌基因发挥作用。

The zinc finger protein560(ZNF560) functions as a novel oncogenic gene in osteosarcoma.

作者信息

Dong Xiong, Xu Guanhua, Hong Hongxiang, Zhang Jinlong, Cui Zhiming, Yu ZiLiang

机构信息

Spinal Surgery Department, The Second Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, P.R. China.

Department of Joint Surgery, The Second Affiliated Hospital of Nantong University, No. 666, ShengLi Road, Chongchuan District, Nantong, 226001, Jiangsu, P.R. China.

出版信息

Sci Rep. 2025 Jan 2;15(1):79. doi: 10.1038/s41598-024-79298-y.

Abstract

BACKGROUND

Abnormal expression of Zinc finger (ZNF) genes is commonly observed in osteosarcoma (OS), the most prevalent malignant bone tumor in children and teenagers. This project focused on the role of ZNF560 in the progress of OS.

METHODS

The published datasets including TCGA-SARC and GSE99671 was utilized to screen out the abnormal expression of ZNF560 and associated gene patterns in sarcoma and OS tissues. Prognosis value of ZNF560 was identified in TCGA-SARC and OS cohorts. In order to manipulate ZNF560 expression in HOS and MG63 osteosarcoma (OS) cells, genetic strategies such as shRNA constructs were utilized. The expression patterns of ZNF560 were analyzed through techniques such as immunohistochemistry, Western blotting, and qRT-PCR.

RESULTS

By analyzing data from both the GEO and the Cancer Genome Atlas (TCGA) databases, increased expression of ZNF560 in OS tissues was verified, which was significantly associated with poorer outcomes in osteosarcoma patients both in TCGA-SARC and our own OS cohorts. Additionally, downregulation of ZNF560 resulted in decreased cell viability, fewer colonies, and induced apoptosis of osteosarcoma cells. Moreover, ZNF560 was found to be essential for migration of human osteosarcoma HOS and MG63 cells.

CONCLUSION

Collectively, these findings suggest that ZNF560 has the potential to serve as a predictive biomarker for osteosarcoma.

摘要

背景

锌指(ZNF)基因的异常表达在骨肉瘤(OS)中普遍存在,骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤。本项目聚焦于ZNF560在骨肉瘤进展中的作用。

方法

利用已发表的数据集,包括TCGA-SARC和GSE99671,筛选出肉瘤和骨肉瘤组织中ZNF560的异常表达及相关基因模式。在TCGA-SARC和骨肉瘤队列中确定ZNF560的预后价值。为了调控人骨肉瘤HOS和MG63细胞中ZNF560的表达,采用了诸如短发夹RNA(shRNA)构建体等基因策略。通过免疫组织化学、蛋白质免疫印迹和实时定量逆转录聚合酶链反应等技术分析ZNF560的表达模式。

结果

通过分析来自基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库的数据,证实骨肉瘤组织中ZNF560表达增加,这在TCGA-SARC和我们自己的骨肉瘤队列中均与骨肉瘤患者较差的预后显著相关。此外,ZNF560的下调导致骨肉瘤细胞活力降低、集落减少并诱导细胞凋亡。而且,发现ZNF560对人骨肉瘤HOS和MG63细胞的迁移至关重要。

结论

总体而言,这些发现表明ZNF560有潜力作为骨肉瘤的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a5a/11696763/efa99d34db32/41598_2024_79298_Figa_HTML.jpg

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