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TICRR过表达增强皮肤黑色素瘤的疾病侵袭性和免疫浸润。

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

作者信息

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

机构信息

Department of Burn and Plastic Surgery, The Second People's Hospital of Yibin (West China Yibin Hospital, Sichuan University), Yibin, Sichuan, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2024 Sep 3;17:423-435. doi: 10.2147/PGPM.S469972. eCollection 2024.

DOI:10.2147/PGPM.S469972
PMID:39246575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11380494/
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.

摘要

目的

研究TopBP1相互作用的检查点和复制调节因子（TICRR）在皮肤黑色素瘤（CM）中作为预后生物标志物和治疗靶点的作用。

方法

利用TCGA和GTEx数据库探索肿瘤样本中TICRR的表达情况。建立Kaplan-Meier生存曲线、列线图模型和风险评分曲线，以评估TICRR在CM中的预后作用。获取CM患者的组织样本以进一步验证TICRR的表达。进行了多项体外实验，以研究TICRR对CM侵袭性的影响并探索潜在机制。

结果

TICRR在CM组织中过表达，且与CM患者的不良预后相关。敲低TICRR可降低CM细胞的增殖、迁移和侵袭能力，而过表达则产生相反的效果。此外，抑制TICRR可显著减弱PI3K/AKT/mTOR信号通路的激活，而PI3K/AKT抑制剂LY294002可部分逆转TICRR过表达诱导的侵袭性增强效应。通过免疫浸润和免疫荧光分析进一步证实，TICRR与免疫细胞浸润活性密切相关。

结论

TICRR过表达可能通过激活PI3K/Akt/mTOR通路和促进免疫浸润来增强CM的侵袭性。TICRR被证实为CM的潜在预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/752ba7ea1cf5/PGPM-17-423-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/1c551e2f26a2/PGPM-17-423-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/738a80ef3967/PGPM-17-423-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/b3a0fce0774c/PGPM-17-423-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/b33edc0c5800/PGPM-17-423-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/f21937c629a1/PGPM-17-423-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/752ba7ea1cf5/PGPM-17-423-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/1c551e2f26a2/PGPM-17-423-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/738a80ef3967/PGPM-17-423-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/b3a0fce0774c/PGPM-17-423-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/b33edc0c5800/PGPM-17-423-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/f21937c629a1/PGPM-17-423-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0fc/11380494/752ba7ea1cf5/PGPM-17-423-g0006.jpg

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本文引用的文献

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Aging (Albany NY). 2024 Jan 11;16(1):911-927. doi: 10.18632/aging.205427.
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serves as a prognostic biomarker in lung adenocarcinoma with implications in RNA epigenetic modification, DDR pathway, and RNA metabolism.作为肺腺癌的一种预后生物标志物，在RNA表观遗传修饰、DNA损伤修复（DDR）途径和RNA代谢中具有重要意义。
Front Oncol. 2023 Dec 13;13:1274439. doi: 10.3389/fonc.2023.1274439. eCollection 2023.
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Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management.
皮肤黑色素瘤：多因素发病机制、免疫组织化学及早期检测和管理新兴生物标志物的综述。
Int J Mol Sci. 2023 Nov 1;24(21):15881. doi: 10.3390/ijms242115881.
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ncRNAs-mediated high expression of TICRR promotes tumor cell proliferation and migration and is correlated with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.ncRNAs介导的TICRR高表达促进肿瘤细胞增殖和迁移，并与肝细胞癌的不良预后和肿瘤免疫浸润相关。
Mol Ther Nucleic Acids. 2022 Sep 19;30:80-94. doi: 10.1016/j.omtn.2022.09.007. eCollection 2022 Dec 13.
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