title: MicroRNA-892b influences proliferation, migration and invasion of bladder cancer cells by mediating the p19ARF/cyclin D1/CDK6 and Sp-1/MMP-9 pathways.
abstract: 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 downregulation 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.
authors: Department of Food Science and Nutrition, Jeju National University, Jeju, Republic of Korea.
authors: Seung-Shick
authors: SS
authors: Shin
authors: Department of Food Science and Nutrition, Jeju National University, Jeju, Republic of Korea.
authors: Sung-Soo
authors: SS
authors: Park
authors: Department of Food and Nutrition, Chung-Ang University, Anseong, Republic of Korea.
authors: Byungdoo
authors: B
authors: Hwang
authors: Department of Food and Nutrition, Chung-Ang University, Anseong, Republic of Korea.
authors: Bokyung
authors: B
authors: Moon
authors: Department of Urology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors: Won Tae
authors: WT
authors: Kim
authors: Department of Urology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors: Wun-Jae
authors: WJ
authors: Kim
authors: Department of Food and Nutrition, Chung-Ang University, Anseong, Republic of Korea.
authors: Sung-Kwon
authors: SK
authors: Moon
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C530104:CCND1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C574666:MIRN892 microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D019938:Cyclin D1; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D020780:Matrix Metalloproteinase 9