MicroRNA-892b influences proliferation, migration and invasion of bladder cancer cells by mediating the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 pathways

• Published in: Oncology reports Vol. 36; no. 4; pp. 2313 - 2320
• Main Authors: Shin, Seung-Shick, Park, Sung-Soo, Hwang, Byungdoo, Moon, Bokyung, Kim, Won Tae, Kim, Wun-Jae, Moon, Sung-Kwon
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2016; Spandidos Publications UK Ltd
• Subjects: Bladder cancer; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cyclin D1 - biosynthesis; Cyclin D1 - genetics; Cyclin-Dependent Kinase 6 - biosynthesis; Cyclin-Dependent Kinase 6 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis; Cyclin-Dependent Kinase Inhibitor p16 - genetics; G1 Phase Cell Cycle Checkpoints - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunoglobulins; Kinases; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Medical prognosis; MicroRNAs; MicroRNAs - genetics; migration; miR-892b; MMP-9; Mutation; Neoplasm Invasiveness - genetics; p19ARF; Proteins; Signal Transduction - genetics; Software; Sp1 Transcription Factor - biosynthesis; Sp1 Transcription Factor - genetics; Studies; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology; United States > US
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2016.5052

Cancers often utilize microRNAs to suppress tumor suppressor genes, thus facilitating their potential for growth and invasion. In the present study, we report the novel findings that miR-892b inhibits proliferation, migration and invasion of bladder cancer cells. The basal expression level of miR-892b was significantly lower in 3 different bladder cancer cell lines than in normal human urothelial cells. Transfection of miR-892b mimics to bladder cancer cells resulted in dose-dependent growth arrest. Flow cytometric analysis of the cell cycle showed that miR-892b-transfected bladder cancer cells were subject to arrest in the G1 phase, which was due to the down-regulation of cyclin D1 and CDK6 followed by upregulation of p19ARF. In addition, overexpression of miR-892b impeded the migration and invasion of EJ cells. Expression of MMP-9 in EJ cells was blocked by transfection of miR-892b; the effect was regulated, at least in part, by activation of the Sp-1 transcription factor. Overall, we verified that miR-892b regulates the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 signaling networks in bladder cancer cells and may provide a treatment option for advanced-stage bladder cancers.