FOXO3a‑modulated DEPDC1 promotes malignant progression of nephroblastoma via the Wnt/β‑catenin signaling pathway

Geng,Geng; Li,Qinghao; Guo,Xingqing; Ni,Qingbin; Xu,Yongtao; Ma,Zhaolong; Wang,Yongjin; Ming,Ming

doi:10.3892/mmr.2022.12788

FOXO3a‑modulated DEPDC1 promotes malignant progression of nephroblastoma via the Wnt/β‑catenin signaling pathway

Authors:
- Geng Geng
- Qinghao Li
- Xingqing Guo
- Qingbin Ni
- Yongtao Xu
- Zhaolong Ma
- Yongjin Wang
- Ming Ming
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Affiliations: Department of Pediatric Surgery, Taian City Central Hospital, Taian, Shandong 271000, P.R. China, Department of Pediatric Respirology and Cardiology, The Affiliated Hospital of Qingdao University, Qingdao 266000, P.R. China
Published online on: July 4, 2022 https://doi.org/10.3892/mmr.2022.12788
Article Number: 272
Copyright: © Geng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

DEP domain containing 1 (DEPDC1) and forkhead box transcription factor 3a (FOXO3a) serve a role in tumor cells. To the best of our knowledge, however, the expression of DEPDC1 and FOXO3a in nephroblastoma and their role and potential mechanisms in nephroblastoma cells have not been reported. The aim of the present study was to characterize the expression of DEPDC1 and FOXO3a in nephroblastoma, as well as the underlying mechanisms. The expression levels of DEPDC1 and FOXO3a were detected using reverse transcription‑quantitative PCR and western blotting. Cell viability, proliferation, invasion and migration were detected using Cell Counting Kit‑8, colony formation, Transwell and wound healing assays, respectively. The activity of DEPDC1 promoter was detected by dual‑luciferase reporter assay and the association between FOXO3a and DEPDC1 was detected using immunoprecipitation. DEPDC1 expression was significantly increased in nephroblastoma cells, particularly WiT49 cells. Compared with the negative control, DEPDC1 knockdown significantly inhibited proliferation, invasion and migration of WiT49 cells, while DEPDC1 overexpression (Ov) reversed these effects. By contrast, expression of FOXO3a was decreased in WiT49 cells and immunoprecipitation showed that FOXO3a bound to the DEPDC1 promoter. Ov‑FOXO3a inhibited WiT49 cell proliferation, invasion and migration, as well as protein expression levels of phosphorylated‑glycogen synthase kinase‑3β, Wnt3a and β‑catenin, while DEPDC1 Ov reversed the inhibitory effects of FOXO3a Ov on WiT49 cells. In conclusion, DEPDC1 promoted malignant progression of nephroblastoma via the Wnt/β‑catenin signaling pathway; this may be regulated by FOXO3a.

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