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多组学分析表明,TAOK1可作为多种肿瘤尤其是宫颈癌的预后标志物和治疗靶点。

Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.

作者信息

Ning Li, Li Xiu, Xu Yating, Si Yu, Zhao Hongting, Ren Qingling

机构信息

The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.

The Chinese Clinical Medicine Innovation Center of Obstetrics, Gynecology, and Reproduction in Jiangsu Province, Nanjing, Jiangsu, People's Republic of China.

出版信息

Onco Targets Ther. 2025 Mar 14;18:335-353. doi: 10.2147/OTT.S506582. eCollection 2025.

Abstract

BACKGROUND

Thousand and One Kinase 1 (TAOK1), a member of the MAPK kinase family, plays a crucial role in processes like microtubule dynamics, DNA damage response, and neurodevelopment. While TAOK1 is linked to tumorigenesis, its oncogenic role across cancers remains unclear. This study aims to explore the relationship between TAOK1 expression, prognosis, and immune function in various cancers.

METHODS

We analyzed TAOK1 expression in multiple cancers using TCGA, GEO, CCLE, and other bioinformatics databases. The correlation between TAOK1 expression and immune cell infiltration was assessed with the ESTIMATE algorithm. We also examined associations with tumor stemness, DNA methylation, gene copy number alterations, and drug sensitivity. The oncogenic role of TAOK1 was further evaluated in vitro with SiHa and A2780 cells and in vivo with TAOK1 overexpression in SiHa cells.

RESULTS

TAOK1 is a key prognostic biomarker in various cancers and its high expression is associated with poor prognosis. It showed a significant negative correlation with immune cell infiltration and immune checkpoints. GSEA identified its involvement in key tumour pathways, highlighting the therapeutic potential of inhibiting the TAOK1 gene. The high expression of TAOK1 is associated with DNA methylation and gene copy number variation, and in addition its upstream regulator, EP300, is closely associated with TAOK1 expression. In vitro cellular experiments demonstrated that inhibition of TAOK1 reduced the proliferation of SiHa and A2780 cells, whereas overexpression of TAOK1 in SiHa cells promoted growth. These findings were further validated in vivo by nude mouse tumourigenicity assay and human tissue immunohistochemistry.

CONCLUSION

TAOK1 serves as a promising prognostic biomarker and potential therapeutic target, especially for cervical cancer. These results support its clinical potential in cancer prognosis and treatment strategies.

摘要

背景

千与一激酶1(TAOK1)是丝裂原活化蛋白激酶激酶家族的成员,在微管动力学、DNA损伤反应和神经发育等过程中起关键作用。虽然TAOK1与肿瘤发生有关,但其在各种癌症中的致癌作用仍不清楚。本研究旨在探讨TAOK1表达、预后与各种癌症免疫功能之间的关系。

方法

我们使用TCGA、GEO、CCLE和其他生物信息学数据库分析了多种癌症中TAOK1的表达。用ESTIMATE算法评估TAOK1表达与免疫细胞浸润之间的相关性。我们还研究了与肿瘤干性、DNA甲基化、基因拷贝数改变和药物敏感性的关联。在体外使用SiHa和A2780细胞,在体内通过在SiHa细胞中过表达TAOK1进一步评估TAOK1的致癌作用。

结果

TAOK1是各种癌症中的关键预后生物标志物,其高表达与预后不良相关。它与免疫细胞浸润和免疫检查点呈显著负相关。基因集富集分析(GSEA)确定其参与关键肿瘤通路,突出了抑制TAOK1基因的治疗潜力。TAOK1的高表达与DNA甲基化和基因拷贝数变异有关,此外其上游调节因子EP300与TAOK1表达密切相关。体外细胞实验表明,抑制TAOK1可降低SiHa和A2780细胞的增殖,而在SiHa细胞中过表达TAOK1则促进生长。这些发现通过裸鼠致瘤性试验和人体组织免疫组化在体内进一步得到验证。

结论

TAOK1是一种有前景的预后生物标志物和潜在治疗靶点,尤其是对宫颈癌。这些结果支持其在癌症预后和治疗策略中的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/11920640/2835ef9a457d/OTT-18-335-g0001.jpg

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