MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma
| Autor: | Zhimao Jiang, Enpu Zhang, Min Shi, Zuhu Yu, Jiongxian Ye, Zhengming Su, Liangchao Ni, Yongqing Lai, Yaoting Gui, Shangqi Yang, Duqun Chen, Yifan Li |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Cancer Research Biology Mitogen-activated protein kinase kinase urologic and male genital diseases Biochemistry MAP3K8 Cell Movement Cell Line Tumor Proto-Oncogene Proteins microRNA Genetics Humans Neoplasm Invasiveness Protein kinase A Carcinoma Renal Cell Molecular Biology Cell Proliferation Gene knockdown Oncogene Cell growth Middle Aged Cell cycle MAP Kinase Kinase Kinases female genital diseases and pregnancy complications Cell biology Gene Expression Regulation Neoplastic MicroRNAs Oncology Gene Knockdown Techniques Cancer research Molecular Medicine Female |
| Zdroj: | Molecular Medicine Reports. |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2015.3498 |
| Popis: | microRNAs (miRNAs; miR) are a class of small non-coding RNA molecules, which are involved in the pathogenesis of human diseases through the negative regulation of gene expression. Previous studies have demonstrated that miR-509-3p is a novel miRNA associated with cell proliferation and migration in 786-O renal cell carcinoma (RCC) cells. However, the mechanism of action of miR-509-3p in RCC remains to be elucidated. The present study aimed to examine the functional role and mechanism of miR-509-3p in the development of RCC. The results demonstrated that the expression levels of miR-509-3p were downregulated in the 786-O and ACHN RCC cell lines compared with the normal tissues of 10 patients with RCC, as determined by reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of mitogen-activated protein kinase kinase kinase 8 (MAP3K8) were upregulated in the RCC cell lines. Functional investigations demonstrated that the overexpression of miR-509-3p inhibited the migration and proliferation of the RCC cells, as determined by wound scratch and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Luciferase reporter assays revealed that the overexpression of miR-509-3p reduced the transcriptional activity of MAP3K8. Furthermore, the present study demonstrated that the ectopic transfection of miR-509-3p led to a significant reduction in the mRNA and protein expression levels of MAP3K8 in the RCC cells. Finally, knockdown of MAP3K8 inhibited the migration and proliferation of the RCC cells. Therefore, the results of the present study demonstrated that the miR-509-3p RCC suppressor was a significant regulator of the MAP3K8 oncogene, suggesting that it may have a potential therapeutic role in the treatment of RCC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|