title: MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer.
abstract: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer.
authors.affiliation: Department of Urology, VA Medical Center and UCSF, San Francisco, California, USA. SMajid@urology.ucsf.edu
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Dar
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Inik
authors.initials: I
authors.lastname: Chang
authors.forename: Kirsten
authors.initials: K
authors.lastname: Greene
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D008156:Luciferases