TICRR Overexpression Enhances Disease Aggressiveness and Immune Infiltration of Cutaneous Melanoma.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI:10.2147/PGPM.S469972

Cheng Chen, Yong Zou, Xiangbing Zheng, Taotao Hu, Jie Ni, Daohong Kan, Zongyin Yin, Lingxiao Ye, Bing Liu

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Abstract

Objective: To investigate the role of the TopBP1 interacting checkpoint and replication regulator (TICRR) in cutaneous melanoma (CM) as a prognostic biomarker and therapeutic target.

Methods: TICRR expression in tumour samples was explored using the TCGA and the GTEx database. The Kaplan-Meier survival curve, nomogram model and risk score curve were established to evaluate the prognostic role of TICRR in CM. Tissue samples of CM patients were obtained to validate the TICRR expression further. Several experiments in vitro were conducted to investigate the effect of TICRR upon CM aggressiveness and to explore underlying mechanisms.

Results: TICRR was overexpressed in CM tissue and was correlated with poor prognosis of CM patients. The knockdown of TICRR decreased the proliferation, migration, and invasion of CM cells, whereas overexpression produced the opposite effect. Furthermore, TICRR suppression substantially attenuated the activation of PI3K/AKT/mTOR signalling, while the PI3K/AKT inhibitor LY294002 could partially reverse the aggressiveness-enhancing effect induced by TICRR overexpression. It was further confirmed that TICRR was closely related to immune cell infiltration activities by using immune infiltration and immunofluorescence analysis.

Conclusion: TICRR overexpression may enhance CM aggressiveness by activating the PI3K/Akt/mTOR pathway and promoting immune infiltration. TICRR was verified as a potential prognostic biomarker and therapeutic target for CM.

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TICRR过表达会增强皮肤黑色素瘤的疾病侵袭性和免疫渗透。

目的研究皮肤黑色素瘤（CM）中作为预后生物标志物和治疗靶点的TopBP1交互检查点和复制调节因子（TICRR）的作用：方法：利用 TCGA 和 GTEx 数据库研究了肿瘤样本中 TICRR 的表达情况。方法：利用 TCGA 和 GTEx 数据库探讨了 TICRR 在肿瘤样本中的表达情况，并建立了 Kaplan-Meier 生存曲线、提名图模型和风险评分曲线，以评估 TICRR 在 CM 中的预后作用。为了进一步验证 TICRR 的表达，研究人员采集了 CM 患者的组织样本。为研究 TICRR 对 CM 侵袭性的影响并探索其潜在机制，进行了多项体外实验：结果：TICRR在CM组织中过表达，并与CM患者的不良预后相关。敲除 TICRR 可减少 CM 细胞的增殖、迁移和侵袭，而过表达则产生相反的效果。此外，TICRR的抑制大大减弱了PI3K/AKT/mTOR信号的激活，而PI3K/AKT抑制剂LY294002能部分逆转TICRR过表达引起的侵袭性增强效应。通过免疫浸润和免疫荧光分析，进一步证实了TICRR与免疫细胞浸润活动密切相关：结论：TICRR的过表达可能会通过激活PI3K/Akt/mTOR通路和促进免疫浸润来增强肿瘤的侵袭性。TICRR被证实是一种潜在的CM预后生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

3.30

自引率

5.30%

发文量

110

审稿时长

16 weeks

期刊介绍： Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.