title: MicroRNA-20b inhibits the proliferation, migration and invasion of bladder cancer EJ cells via the targeting of cell cycle regulation and Sp-1-mediated MMP-2 expression.
abstract: MicroRNAs (miRs) serve either as oncogenes or tumor-suppressor genes in tumor progression. MicroRNA-20b (miR‑20b) is known to be involved with the oncomirs of several types of cancers. However, in the present study we describe how miR-20b inhibits the proliferation, migration and invasion of bladder cancer EJ cells. In the present study, miR-20b was downregulated in bladder cancer cell lines, and its overexpression resulted in a significant reduction in the proliferation of EJ cells. In addition, via a bioinformatics approach, we identified cell cycle-regulated genes that are the putative targets of miR-20b. The transfection of miR-20b into EJ cells induced G1 phase cell cycle arrest via the decreased expression of cyclin D1, CDK2 and CDK6 without affecting another G1 phase cell cycle regulator, cyclin E. The cell cycle inhibitor p21WAF1 was upregulated in the miR-20b transfected cells. Moreover, the enforced expression of miR-20b resulted in impaired wound-healing migration and invasion in the EJ cells. Based on our target prediction analysis of miRs, we confirmed that miR-20b overexpression strongly impedes MMP-2 expression via suppressive activation of the Sp-1 binding motif, an important transcription factor present in the MMP-2 promoter. Herein, we report the novel concept that miR-20b exerts a suppressive effect on both cell cycle-modulated proliferation and MMP-2-mediated migration and invasion in bladder cancer EJ cells.
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Sung Lyea
authors.initials: SL
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Cho
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Se Yeon
authors.initials: SY
authors.lastname: Won
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Song
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Dae-Hwa
authors.initials: DH
authors.lastname: Noh
authors.affiliation: Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis; D051361:Cyclin-Dependent Kinase 6 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C530104:CCND1 protein, human; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D020778:Matrix Metalloproteinase 2