免疫治疗靶点ANLN通过调节PI3K/Akt和P53信号通路促进肾透明细胞癌

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2025-05-24 DOI:10.1002/biof.70023
Li Shan, Guo-jian Gu, Cheng-Cheng Xiang, Er-Dong Zuo, Lian Lian, Xu Cheng
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引用次数: 0

摘要

Anillin (ANLN)在透明细胞肾细胞癌(ccRCC)中的作用尚不清楚。本研究旨在探讨ANLN在ccRCC中的可能作用及机制。通过使用来自癌症基因组图谱(TCGA)的数据,我们评估了各种癌症中ANLN的表达。此外,GEPIA数据库用于分析存活率、途径富集和免疫浸润。通过实验研究ANLN表达对肿瘤细胞凋亡、迁移、侵袭和增殖的影响。通过蛋白印迹检测细胞凋亡、增殖、上皮间充质转化(epithelial mesenchymal transition, EMT)以及PI3K/AKT和P53信号通路相关蛋白的表达。TCGA数据库显示,在不同的癌症组织中,ANLN的mRNA水平显著升高,在ccRCC患者中也观察到这一发现。值得注意的是,在ccRCC患者中,高ANLN水平与较低的病理分级和较差的生存预后相关。体外实验表明,在ccRCC细胞中,敲低ANLN可导致增殖、迁移、侵袭和EMT的减少。此外,基于免疫浸润分析,ANLN似乎影响免疫逃避并增加远处转移的可能性。使用PI3K/AKT通路抑制剂或P53信号通路激动剂可有效减少ccRCC的侵袭行为并纠正免疫抑制。总之,ANLN可能是ccRCC患者生存的一个有价值的预后指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Immunotherapeutic Target ANLN Promotes Renal Clear Cell Carcinoma by Regulating PI3K/Akt and P53 Signaling Pathways

The role of Anillin (ANLN) in clear cell renal cell carcinoma (ccRCC) is not well understood. This study aimed to investigate the possible function and mechanism of ANLN in ccRCC. By using data from the Cancer Genome Atlas (TCGA), we assessed ANLN expression in various cancers. Furthermore, the GEPIA database was used to analyze survival rates, pathway enrichment, and immune infiltration. Experiments were employed to study how ANLN expression affects tumor cell apoptosis, migration, invasion, and proliferation. Protein blotting was conducted to evaluate apoptosis, proliferation, epithelial mesenchymal transition (EMT), and the expression of proteins linked to the PI3K/AKT and P53 signaling pathways. mRNA levels of ANLN were notably increased in diverse cancer tissues, as shown in the TCGA database, a finding that was also observed in ccRCC patients. Remarkably, high ANLN levels were associated with lower pathologic grades and a worse survival prognosis in ccRCC patients. In vitro experiments revealed that knockdown of ANLN in ccRCC cells led to reduced proliferation, migration, invasion, and EMT. Additionally, ANLN seemed to impact immune evasion and increase the likelihood of distant metastasis based on immune infiltration analyses. The use of PI3K/AKT pathway inhibitors or P53 signaling pathway agonists was effective in reducing the invasive behavior of ccRCC and correcting immunosuppression. Overall, ANLN could be a valuable prognostic indicator for the survival of ccRCC patients.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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