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

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.