miR‑223‑3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors

Liu,Jikai; Shi,Hao; Li,Xidan; Chen,Gang; Larsson,Catharina; Lui,Weng-Onn

doi:10.3892/ijo.2016.3807

miR‑223‑3p regulates cell growth and apoptosis via FBXW7 suggesting an oncogenic role in human testicular germ cell tumors

Authors:
- Jikai Liu
- Hao Shi
- Xidan Li
- Gang Chen
- Catharina Larsson
- Weng-Onn Lui
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Affiliations: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE‑171 76 Stockholm, Sweden, Department of Medicine-Huddinge, Karolinska University Hospital-Huddinge, SE-141 86 Stockholm, Sweden, Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China
Published online on: December 15, 2016 https://doi.org/10.3892/ijo.2016.3807
Pages: 356-364
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

miR‑223‑3p is deregulated in several tumor types and plays an important role in tumorigenesis and progression. However, its role in the pathogenesis of testicular germ cell tumor (TGCT) remains uncharacterized. We previously demonstrated that miR‑223‑3p expression was increased in TGCTs compared with normal testes (NT), suggesting that miR‑223‑3p may have an oncogenic role in TGCT. Using published dataset and The Cancer Genome Atlas database, we validated higher miR‑223‑3p expression in TGCTs than NT, and found a negative correlation between miR-223-3p and FBXW7 mRNA expression levels. Using both gain- and loss-of-function experiments, we show that miR‑223‑3p regulates FBXW7 protein expression, cell growth and apoptosis in TGCT cell lines. Additionally, we demonstrate that ectopic expression of the full-length coding sequence of FBXW7 could rescue the cell growth and apoptotic effects mediated by miR‑223‑3p. Our findings suggest an oncogenic role for miR‑223‑3p in TGCT, which promotes cell growth and inhibits apoptosis through repression of FBXW7.

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