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FOXM1/KIF20A轴通过调节上皮-间质转化信号促进肾透明细胞癌进展并影响免疫治疗反应。

FOXM1/KIF20A axis promotes clear cell renal cell carcinoma progression via regulating EMT signaling and affects immunotherapy response.

作者信息

Fang Kai, Gong Min, Liu Dong, Liang Shengjie, Li Yang, Sang Weicong, Zhu Rujian

机构信息

Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Heliyon. 2023 Nov 23;9(12):e22734. doi: 10.1016/j.heliyon.2023.e22734. eCollection 2023 Dec.

Abstract

BACKGROUND

The correlation between FOXM1 and KIF20A has not been revealed in clear cell renal cell carcinoma (ccRCC).

METHODS

Public data was downloaded from The Cancer Genome Atlas (TCGA) database. R software was utilized for the execution of bioinformatic analysis. The expression levels of specific molecules (mRNA and protein) were detected using real-time quantitative PCR (qRT-PCR) and Western blot assays. The capacity of cell growth was assessed by employing CCK8 and colony formation assay. Cell invasion and migration ability were assessed using transwell assay.

RESULTS

In our study, we illustrated the association between FOXM1 and KIF20A. Our results indicated that both FOXM1 and KIF20A were associated with poor prognosis and clinical performance. The malignant characteristics of ccRCC cells can be significantly suppressed by inhibiting FOXM1 and KIF20A, as demonstrated by in vitro experiments. Moreover, we found that FOXM1 can upregulate KIF20A. Then, EMT signaling was identified as the underlying pathway FOXM1 and KIF20A are involved. WB results indicated that FOXM1/KIF20A axis can activate EMT signaling. Moreover, we noticed that FOXM1 and KIF20A can affect the immunotherapy response and immune microenvironment of ccRCC patients.

CONCLUSIONS

Our results identified the role of the FOXM1/KIF20A axis in ccRCC progression and immunotherapy, making it the underlying target for ccRCC.

摘要

背景

在透明细胞肾细胞癌(ccRCC)中,FOXM1与KIF20A之间的相关性尚未明确。

方法

从癌症基因组图谱(TCGA)数据库下载公开数据。利用R软件进行生物信息学分析。使用实时定量PCR(qRT-PCR)和蛋白质免疫印迹法检测特定分子(mRNA和蛋白质)的表达水平。采用CCK8和集落形成试验评估细胞生长能力。使用Transwell试验评估细胞侵袭和迁移能力。

结果

在我们的研究中,阐述了FOXM1与KIF20A之间的关联。我们的结果表明,FOXM1和KIF20A均与不良预后和临床表现相关。体外实验表明,抑制FOXM1和KIF20A可显著抑制ccRCC细胞的恶性特征。此外,我们发现FOXM1可上调KIF20A。随后,确定EMT信号通路是FOXM1和KIF20A所涉及的潜在通路。蛋白质免疫印迹结果表明,FOXM1/KIF20A轴可激活EMT信号通路。此外,我们注意到FOXM1和KIF20A可影响ccRCC患者的免疫治疗反应和免疫微环境。

结论

我们的结果确定了FOXM1/KIF20A轴在ccRCC进展和免疫治疗中的作用,使其成为ccRCC的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dee8/10730723/7795f37b49b4/gr1.jpg

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