Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Oncology Research Laboratory, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an 710061, China.
Int J Mol Sci. 2023 Aug 1;24(15):12301. doi: 10.3390/ijms241512301.
Forkhead box protein P3 () primarily functions as the master regulator in regulatory T cells (Tregs) differentiation, but its high level of expression has also been found in tumor cells recently. The aim of our study was to clarify the role of in renal cell carcinoma (RCC) progression and metastasis. We verified the characteristic clinicopathological data from The Cancer Genome Atlas (TCGA) database using bioinformatics tools. Meanwhile, RNA sequencing was performed to determine the biofunction in RCC progression. Our results showed that high expression of was found in - or -mutant patients with RCC, and a higher expression was related to worse prognosis. However, there was no statistically significant relationship between the IHC score and RCC malignant progression owning to the limited number of patients in our tissue microarray. Using in vitro loss-of-function assays, we verified that silencing in 786-O and ACHN cells could inhibit the cell migration/invasion capability, which was consistent with the data from RNA sequencing in 786-O cells and from the TCGA datasets. Using an in vivo nude mice orthotopic kidney cancer model, we found that silencing could inhibit tumor growth. In conclusion, our study demonstrated that or mutation could lead to higher expression of in RCC patients, and could eventually stimulate RCC cells' invasion and metastasis, which might indicate that could function as a potential oncogene in RCC progression.
叉头框蛋白 P3 () 主要作为调节性 T 细胞 (Tregs) 分化的主调控因子发挥作用,但最近也在肿瘤细胞中发现其高表达。我们的研究旨在阐明在肾细胞癌 (RCC) 进展和转移中的作用。我们使用生物信息学工具验证了来自癌症基因组图谱 (TCGA) 数据库的特征临床病理数据。同时,进行了 RNA 测序以确定在 RCC 进展中的功能。我们的结果表明,在具有 RCC 的 -或-突变患者中发现了高表达,并且较高的表达与预后较差相关。然而,由于我们的组织微阵列中患者数量有限,IHC 评分与 RCC 恶性进展之间没有统计学上的显著关系。通过体外功能丧失测定,我们验证了在 786-O 和 ACHN 细胞中沉默可以抑制细胞迁移/侵袭能力,这与 786-O 细胞中的 RNA 测序数据以及 TCGA 数据集的数据一致。通过体内裸鼠原位肾癌模型,我们发现沉默可以抑制肿瘤生长。总之,我们的研究表明,或突变可能导致 RCC 患者中更高的表达,并且最终可能刺激 RCC 细胞的侵袭和转移,这可能表明在 RCC 进展中可以作为潜在的癌基因。