title: MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer.
abstract: The Wnt/beta-catenin (CTNNB1) and Ras-Raf-MEK-ERK signaling pathway play an important role in bladder cancer (BC) progression. Tumor-suppressive microRNAs (miRNAs) targeting these cancer pathways may provide a new therapeutic approach for BC. We initially identified miRNA-1826 potentially targeting CTNNB1, VEGFC and MEK1 using several target scan algorithms. Also 3' untranslated region luciferase activity and protein expression of these target genes were significantly downregulated in miR-1826-transfected BC cells (J82 and T24). The expression of miR-1826 was lower in BC tissues and inverse correlation of miR-1826 with several clinical parameters (pT, grade) was observed. Also the expression of miR-1826 was much lower in three BC cell lines (J82, T24 and TCCSUP) compared with a normal bladder cell line (SV-HUC-1). We then performed analyses to look at miR-1826 function and found that miR-1826 inhibited BC cell viability, invasion and migration. We also found increased apoptosis and G(1) cell cycle arrest in miR-1826-transfected BC cells. To examine whether the effect of miR-1826 was through CTNNB1 (beta-catenin) or MEK1 knockdown, we knocked down CTNNB1/MEK1 messenger RNA using a small interfering RNA (siRNA) technique. We observed that CTNNB1 or MEK1 siRNA knockdown resulted in effects similar to those with miR-1826 in BC cells. In conclusion, our data suggest that the miR-1826 plays an important role as tumor suppressor via CTNNB1/MEK1/VEGFC downregulation in BC.
authors: Department of Urology, San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121, USA.
authors: Hiroshi
authors: H
authors: Hirata
authors: Yuji
authors: Y
authors: Hinoda
authors: Koji
authors: K
authors: Ueno
authors: Varahram
authors: V
authors: Shahryari
authors: Z Laura
authors: ZL
authors: Tabatabai
authors: Rajvir
authors: R
authors: Dahiya
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D042582:Vascular Endothelial Growth Factor C / Q000037:antagonists & inhibitors* / Q000235:genetics; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; C570042:MIRN1826 microRNA, human; D035683:MicroRNAs; D042582:Vascular Endothelial Growth Factor C; D051176:beta Catenin; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human