title: Nephroblastomas show low expression of microR-204 and high expression of its target, the oncogenic transcription factor MEIS1.
abstract: By comparing several studies we identified a possible deregulation of the transcription factors PBX2 (pre-B-cell leukemia homeobox 2) and one of its binding partners, MEIS1 (Meis homeobox 1) in nephroblastomas. The regulation of MEIS1 is complex, and its expression is known to be influenced by changes of promoter methylation and binding of microRNA-204 (miR-204). Therefore, in our study, we assessed the expression of MEIS1 and PBX2 and the factors regulating expression of MEIS1 in nephroblastomas. MEIS1 and PBX2 messenger RNA (mRNA) and protein levels were investigated by quantitative real-time-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Promoter methylation of MEIS1 was evaluated using a methylation-specific PCR assay. Expression levels of miR-204 were examined by qRT-PCR. Eighteen of 21 nephroblastomas showed a high level of MEIS1 mRNA, and 22 of 26 samples had a specific nuclear protein expression. MicroRNA-204 had a statistically significantly lower expression in all nephroblastomas investigated compared with renal parenchyma, but no change of MEIS1 promoter methylation status was noted. Eleven of 23 nephroblastomas had a high expression of PBX2 mRNA, and 15 of 23 samples had a specific nuclear protein expression was noted. In our study, we demonstrated an expression of MEIS1 and its binding partner PBX2 in most nephroblastomas. The statistically significantly lower expression of miR-204 in all nephroblastomas investigated might point to an involvement of miR-204 in the regulation of MEIS1 in nephroblastomas.
authors.affiliation: 1  Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Koller
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Karin
authors.initials: K
authors.lastname: Koch
authors.forename: Martina
authors.initials: M
authors.lastname: Zandl
authors.forename: Verena
authors.initials: V
authors.lastname: Stiegelbauer
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.forename: Barbara
authors.initials: B
authors.lastname: Guertl
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C090465:PBX2 protein, human; D011518:Proto-Oncogene Proteins
keywords: MEIS1; PBX2; miR-204; nephroblastoma