RESUMO
Wilms' tumor is the most common type of renal tumor in children. MicroRNAs (miRNAs) are small noncoding RNAs that play crucial regulatory roles in tumorigenesis. We aimed to study the expression profile and function of miR-27a-5p in Wilms' tumor. miR-27a-5p expression was downregulated in human Wilms' tumor tissues. Functionally, overexpression of miR-27a-5p promoted cell apoptosis of Wilms' tumor cells. Furthermore, upregulated miR-27a-5p delayed xenograft Wilms' tumor tumorigenesis in vivo. Bioinformatics analysis predicted that miR-27a-5p directly targeted the 3'-untranslated region (3'-UTR) of PBOV1, and luciferase reporter assay confirmed the interaction between miR-27a-5p and PBOV1. The function of PBOV1 in Wilms' tumor was evaluated in vitro, and knockdown of PBOV1 dampened cell migration. In addition, overexpression of PBOV1 antagonized the tumor-suppressive effect of miR-27a-5p in Wilms' tumor cells. Collectively, our findings reveal the regulatory axis of miR-27a-5p/PBOV1 in Wilms' tumor, and miR-27a-5p might serve as a novel therapeutic target in Wilms' tumor.
Assuntos
Neoplasias Renais , MicroRNAs , Tumor de Wilms , Apoptose/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Tumor de Wilms/genética , Tumor de Wilms/metabolismo , Tumor de Wilms/patologiaRESUMO
Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children. Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) is an identified cancer-associated lncRNA that plays an important role in various cancers. However, the role of DLEU1 in Wilms tumor remains unclear. In the present study, we examined the expression and role of DLEU1 in Wilms tumor. We demonstrated that DLEU1 expression was upregulated in Wilms tumor tissues and cell lines. Knockdown of DLEU1 significantly inhibited the proliferation, migration and invasion of GHINK-1 cells. Furthermore, DLEU1 directly sponged miR-300 and regulated the expression level of miR-300 in GHINK-1 cells. Inhibition of miR-300 reversed the inhibitory effects of DLEU1 downregulation on cell proliferation, migration and invasion. Homeobox C8 (HOXC8) was found to be a target gene of miR-300 and mediated the role of miR-300 in GHINK-1 cells. In conclusion, these findings indicated that DLEU1 executed an oncogenic role in Wilms tumor via regulating the miR-300/HOXC8 axis, indicating that DLEU1 might be a therapeutic target for the treatment of Wilms tumor.
