FOXO3a inhibits nephroblastoma cell proliferation, migration and invasion, and induces apoptosis through downregulating the Wnt/β‑catenin signaling pathway
Affiliations: Department of Pediatric Surgery, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277102, P.R. China, Department of Urinary Surgery, The Second People's Hospital of Nantong, Nantong, Jiangsu 226002, P.R. China
- Published online on: September 13, 2021 https://doi.org/10.3892/mmr.2021.12436
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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.