title: 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.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE‑171 76 Stockholm, Sweden.
authors.forename: Jikai
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE‑171 76 Stockholm, Sweden.
authors.forename: Hao
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Medicine-Huddinge, Karolinska University Hospital-Huddinge, SE-141 86 Stockholm, Sweden.
authors.forename: Xidan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE‑171 76 Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE‑171 76 Stockholm, Sweden.
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D044783:F-Box Proteins / Q000096:biosynthesis* / Q000235:genetics; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; D035683:MicroRNAs; D044767:Ubiquitin-Protein Ligases; C513273:FBXW7 protein, human; C525067:MIR223, human