RESUMO
PURPOSE: The aim of this study was to detect candidate oncogenes of rhabdoid tumor of the kidney (RTK) and evaluate their roles in RTK in vitro. METHODS: An integrated analysis of messenger RNA (mRNA) and microRNA (miRNA) sequencing was performed to determine the expression profile of exosome-derived miRNAs and mRNAs in human RTK-derived cell lines and a human embryonic renal cell line. A Gene Ontology enrichment analysis was performed to analyze the functional characteristics of differentially expressed mRNAs in RTK cells. Matrigel invasion and wound-healing assays were performed to evaluate the cell invasion and migration abilities. RESULTS: Forty mRNAs were highly expressed in RTK cells targeted by exosomal miRNAs, the expression of which was lower in RTK cells than in the controls. These mRNAs were primarily related to cell adhesion. Of these mRNAs, we selected neuropilin 1 (NRP1) as a candidate oncogene because its upregulated expression is associated with a poor prognosis of several types of tumors. RTK cells in which NRP1 had been knocked down exhibited decreased invasive and migratory abilities. CONCLUSION: Our study indicates that NRP1 acts as an oncogene by promoting the invasion and migration of RTK cells and that it could serve as a therapeutic target.
Assuntos
Movimento Celular , Neoplasias Renais , Invasividade Neoplásica , Neuropilina-1 , Tumor Rabdoide , Humanos , Neuropilina-1/genética , Neuropilina-1/metabolismo , Movimento Celular/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Invasividade Neoplásica/genética , Tumor Rabdoide/genética , Tumor Rabdoide/patologia , Linhagem Celular Tumoral , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Técnicas de Silenciamento de Genes/métodosRESUMO
TFAP2E is a member of the activator protein-2 transcription factor family and acts as a tumor suppressor in several types of cancer. Downregulation of TFAP2E expression is significantly associated with a shorter overall survival period in patients with oral squamous cell carcinoma (OSCC). To evaluate the molecular mechanisms by which TFAP2E suppresses the development or progression of OSCC, the present study investigated the effects of TFAP2E downregulation on OSCC-derived Ca9-22 and HSC-4 cells. The present study demonstrated that small interfering RNA mediated-knockdown of TFAP2E accelerated the proliferation of these OSCC cell lines compared with that in the control group, as determined by the standard water-soluble tetrazolium salt-8 assay. To analyze the cell cycle progression rate, the cell cycle distribution patterns of TFAP2E-knockdown and control cells cultured in the presence of nocodazole, which prevents the completion of mitosis, were analyzed by fluorescence-activated cell sorting at different time points. When analyzing cellular DNA contents, no major differences in cell cycle profiles were observed; however, the rate of increase in cells positive for histone H3 Serine 28 phosphorylation, a standard molecular marker of early M phase, was significantly higher in TFAP2E-knockdown cells than in the control cells. Collectively, these results suggested that TFAP2E may attenuate the proliferation of OSCC cells by regulating G2/M transition.