Forkhead transcription factor O subfamily 3A (FOXO3a) is an important tumor suppressor gene that is expressed in renal tissue and has been reported to be downregulated in clear cell renal cell carcinoma (CCRCC). Notably, the overexpression of FOXO3a was previously discovered to inhibit the progression of CCRCC. However, the expression levels of FOXO3a in nephroblastoma cell lines remain unknown. The present study aimed to investigate the expression levels of FOXO3a in nephroblastoma cell lines and to determine the mechanism of action of the biological functions of FOXO3a. Western blotting and reverse transcription‑quantitative PCR were used to analyze the expression levels of FOXO3a in nephroblastoma cell lines. Subsequently, the effects of the overexpression of FOXO3a and the genetic knockdown of the Wnt/β‑catenin signaling protein Axin‑2 on the biological functions were determined through Cell Counting Kit‑8, cell colony formation assays, scratch and Transwell assay and flow cytometric analysis experiments. The expression levels of FOXO3a were discovered to be downregulated in nephroblastoma cell lines. The overexpression of FOXO3a inhibited the proliferation, invasion and migration of nephroblastoma cells, while inducing apoptosis. Furthermore, the overexpression of FOXO3a downregulated the expression levels of β‑catenin and Cyclin‑D1 proteins involved in the Wnt/β‑catenin signaling pathway. Cell proliferation and the migration and invasion ability of 17‑94 cells in shRNA‑Axin2‑2 group were promoted. Cell apoptosis was predominantly increased by overexpressed FOXO3a, which was reversed by shRNA‑Axin2‑1. The biological effects of overexpressing FOXO3a on nephroblastoma were reversed after activation of Wnt/β‑catenin. In conclusion, the findings of the present study suggested that FOXO3a may inhibit nephroblastoma cell proliferation, migration and invasion, while inducing apoptosis, by downregulating the Wnt/β‑catenin signaling pathway. These results may provide a novel method for the early diagnosis and precise treatment of nephroblastoma.

中文翻译：

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FOXO3a 通过下调 Wn​​t/β-catenin 信号通路抑制肾母细胞瘤细胞增殖、迁移和侵袭，并诱导细胞凋亡。

Forkhead 转录因子 O 亚家族 3A (FOXO3a) 是一种重要的肿瘤抑制基因，在肾组织中表达，据报道在透明细胞肾细胞癌 (CCRCC) 中下调。值得注意的是，先前发现 FOXO3a 的过表达可抑制 CCRCC 的进展。然而，FOXO3a 在肾母细胞瘤细胞系中的表达水平仍然未知。本研究旨在研究 FOXO3a 在肾母细胞瘤细胞系中的表达水平，并确定 FOXO3a 生物学功能的作用机制。Western印迹和逆转录定量PCR用于分析FOXO3a在肾母细胞瘤细胞系中的表达水平。随后，FOXO3a过表达和Wnt/β-catenin信号蛋白Axin-2基因敲低对生物学功能的影响通过Cell Counting Kit-8、细胞集落形成试验、Scratch and Transwell试验和流式细胞仪分析实验确定. 发现 FOXO3a 的表达水平在肾母细胞瘤细胞系中下调。FOXO3a的过表达抑制肾母细胞瘤细胞的增殖、侵袭和迁移，同时诱导细胞凋亡。此外，FOXO3a 的过表达下调了参与 Wnt/β-catenin 信号通路的 β-catenin 和 Cyclin-D1 蛋白的表达水平。促进shRNA-Axin2-2组17-94个细胞的增殖和迁移侵袭能力。细胞凋亡主要由过表达的 FOXO3a 增加，而 shRNA-Axin2-1 可逆转这种情况。在激活 Wnt/β-catenin 后，过表达 FOXO3a 对肾母细胞瘤的生物学效应被逆转。总之，本研究结果表明，FOXO3a 可能通过下调 Wn​​t/β-catenin 信号通路抑制肾母细胞瘤细胞增殖、迁移和侵袭，同时诱导细胞凋亡。这些结果可能为肾母细胞瘤的早期诊断和精准治疗提供一种新的方法。在诱导细胞凋亡的同时，通过下调 Wn​​t/β-catenin 信号通路。这些结果可能为肾母细胞瘤的早期诊断和精准治疗提供一种新的方法。在诱导细胞凋亡的同时，通过下调 Wn​​t/β-catenin 信号通路。这些结果可能为肾母细胞瘤的早期诊断和精准治疗提供一种新的方法。