MicroRNA-197 Mediates the Overgrowth and Anti-Apoptotic Effects by Downregulating Insulin-Like Growth Factor-Binding Protein-3 During Nephroblastoma Tumorigenesis.
Fetal Pediatr Pathol
; 35(5): 287-298, 2016.
Article
en En
| MEDLINE
| ID: mdl-27223680
ABSTRACT
MiR-197 is frequently upregulated to induce a series of oncogenic effects, which is closely associated with poor survival and prognosis of multiple malignancies. However, the roles of miR-197 in tumorigenesis and the detailed molecular mechanism in Wilms tumor (WT) have rarely been reported. This study aimed to evaluate the expression of miR-197 in WT in vivo and the potential effects of miR-197 on the proliferation and apoptosis in SK-NEP-1 cells. A total of 15 patients with a pathologically confirmed diagnosis of WT and 15 paraneoplastic controls were enrolled. Real-time quantitative PCR (RT-qPCR) identified the upregulation of miR-197 and downregulation of insulin-like growth factors binding protein 3 (IGFBP3) in WT tissues in comparison with adjacent normal tissue (p < 0.001). CCK-8 and flow cytometry assay found that inhibition of miR-197 caused a significantly reduced proliferation along with a dramatically enhanced apoptosis of SK-NEP-1 cells (p < 0.01). IGFBP3 was overexpressed in SK-NEP-1 cells by pEGFP-C1-IGFBP3 plasmid transfection. Overexpression of IGFBP3 suppressed the proliferation and induced the apoptosis of SK-NEP-1 cells (p < 0.01). Further study detected the decreased IGFBP3 expression with miR-197 mimics SK-NEP-1 cells and increased IGFBP3 expression with miR-197 inhibitor SK-NEP-1 cells compared with mock (p < 0.01). Dual luciferase reporter assay revealed a direct interaction between miR-197 and 3'-UTR site of IGFBP3. Overall, the above results indicated that miR-197 targeted IGFBP3 to induce the overgrowth and anti-apoptotic effects of WT cells, which could promote nephroblastoma tumorigenesis. Therefore, miR-197 may be further assessed as a potential target for the treatment of WT.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación Neoplásica de la Expresión Génica
/
Tumor de Wilms
/
Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
/
MicroARNs
/
Neoplasias Renales
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Fetal Pediatr Pathol
Asunto de la revista:
PATOLOGIA
/
PEDIATRIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
China