title: Dicer ablation promotes a mesenchymal and invasive phenotype in bladder cancer cells.
abstract: Dicer expression is frequently altered in cancer and affects a wide array of cellular functions acting as an oncogene or tumor suppressor in varying contexts. It has been shown that Dicer expression is also deregulated in urothelial cell carcinoma of the bladder (UCCB) but the nature of this deregulation differs between reports. The aim of the present study was to gain a better understanding of the role of Dicer in bladder cancer to help determine its contribution to the disease. The results showed that Dicer transcript levels were decreased in UCCB tumor tissues as compared to normal tissues, suggesting that Dicer is a tumor suppressor. However, consistent with previous results, we demonstrated that knockdown of Dicer decreases cell viability and increases the induction of apoptosis, suggesting that Dicer is an oncogene. To resolve this discrepancy, we assessed the effects of decreased Dicer expression on epithelial-to‑mesenchymal transition, migration and invasion. We showed that decreased Dicer levels promoted a mesenchymal phenotype and increased migration. Additionally, the results showed that Dicer protein ablation leads to increased cell invasion, higher levels of matrix metalloproteinase-2, and decreased levels of key miRNAs shown to inhibit invasion. The results of this study suggest that decreased Dicer levels may portend a more malignant phenotype.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Lombard
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Lim
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Nakagawa
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Vidallo
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Libertini
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Platero
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Mudryj
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D043244:Ribonuclease III / Q000096:biosynthesis / Q000235:genetics*; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; C408087:DICER1 protein, human; D043244:Ribonuclease III; D020778:Matrix Metalloproteinase 2; D053487:DEAD-box RNA Helicases