title: Glucocorticoid receptor beta increases migration of human bladder cancer cells.
abstract: Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p < 0.05) increased expression of GRβ compared to UMUC-3, which also correlated with higher migration rates. Knockdown of GRβ in the T24 cells resulted in a decreased migration rate. Mutational analysis of the 3' untranslated region (UTR) of human GRβ revealed that miR144 might positively regulate expression. Indeed, overexpression of miR144 increased GRβ by 3.8 fold. In addition, miR144 and GRβ were upregulated during migration. We used a peptide nucleic acid conjugated to a cell penetrating-peptide (Sweet-P) to block the binding site for miR144 in the 3'UTR of GRβ. Sweet-P effectively prevented miR144 actions and decreased GRβ expression, as well as the migration of the T24 human bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Lucien
authors.initials: L
authors.lastname: McBeth
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Assumpta C
authors.initials: AC
authors.lastname: Nwaneri
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Grabnar
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Demeter
authors.affiliation: Advanced Microscopy and Imaging Center, Department of Surgery, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nestor-Kalinoski
authors.affiliation: Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Terry D
authors.initials: TD
authors.lastname: Hinds
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D018613:Microscopy, Confocal; D034622:RNA Interference; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D005938:Glucocorticoids; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D003907:Dexamethasone
keywords: GR; GR alpha; GR beta; glucocorticoid receptor; glucocorticoids