title: MicroRNA-197 Mediates the Overgrowth and Anti-Apoptotic Effects by Downregulating Insulin-Like Growth Factor-Binding Protein-3 During Nephroblastoma Tumorigenesis.
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.
authors.affiliation: a Department of Pediatric Surgery , Guangzhou Women and Children's Medical Center , Guangzhou , Guangdong , China.|b Jinan University , Guangzhou , Guangdong , China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Department of Pediatric Surgery , Guangzhou Women and Children's Medical Center , Guangzhou , Guangdong , China.
authors.forename: Guochang
authors.initials: G
authors.lastname: Liu
authors.affiliation: a Department of Pediatric Surgery , Guangzhou Women and Children's Medical Center , Guangzhou , Guangdong , China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: a Department of Pediatric Surgery , Guangzhou Women and Children's Medical Center , Guangzhou , Guangdong , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: a Department of Pediatric Surgery , Guangzhou Women and Children's Medical Center , Guangzhou , Guangdong , China.|b Jinan University , Guangzhou , Guangdong , China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D063646:Carcinogenesis; D049109:Cell Proliferation / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology*
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C546085:MIRN197 microRNA, human; D035683:MicroRNAs
keywords: Wilms tumor; apoptosis; insulin-like growth factors binding protein 3; miR-197; proliferation