title: Monocyte Chemoattractant Protein-Induced Protein 1 Overexpression Modulates Transcriptome, Including MicroRNA, in Human Neuroblastoma Cells.
abstract: The recently discovered MCPIP1 (monocyte chemoattractant protein-induced protein 1), a multidomain protein encoded by the MCPIP1 (ZC3H12A) gene, has been described as a new differentiation factor, a ribonuclease, and a deubiquitination-supporting factor. However, its role in cancer is poorly recognized. Our recent analysis of microarrays data showed a lack of expression of the MCPIP1 transcript in primary neuroblastoma, the most common extracranial solid tumor in children. Additionally, enforced expression of the MCPIP1 gene in BE(2)-C cells caused a significant decrease in neuroblastoma proliferation and viability. Aim of the present study was to further investigate the role of MCPIP1 in neuroblastoma, using expression DNA microarrays and microRNA microarrays. Transient transfections of BE(2)-C cells were used for overexpression of either wild type of MCPIP1 (MCPIP1-wt) or its RN-ase defective mutant (MCPIP1-ΔPIN). We have analyzed changes of transcriptome and next, we have used qRT-PCR to verify mRNA levels of selected genes responding to MCPIP1 overexpression. Additionally, protein levels were determined for some of the selected genes. The choline transporter, CTL1, encoded by the SLC44A1 gene, was significantly repressed at the specific mRNA and protein levels and most importantly this translated into a decreased choline transport in MCPIP1-overexpressing cells. Then, we have found microRNA-3613-3p as the mostly altered in the pools of cells overexpressing the wild type MCPIP1. Next, we analyzed the predicted targets of the miR-3613-3p and validated them using qRT-PCR and western blot. These results indicate that the expression of miR-3613-3p might be regulated by MCPIP1 by cleavage of its precursor form.
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Elżbieta
authors: E
authors: Boratyn
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Iwona
authors: I
authors: Nowak
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Irena
authors: I
authors: Horwacik
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Małgorzata
authors: M
authors: Durbas
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Anna
authors: A
authors: Mistarz
authors: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Magdalena
authors: M
authors: Kukla
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Przemysław
authors: P
authors: Kaczówka
authors: Department of Pathology, Institute "Pomnik - Centrum Zdrowia Dziecka", Aleja Dzieci Polskich 20, Warszawa, 04-730, Poland.
authors: Maria
authors: M
authors: Łastowska
authors: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Jolanta
authors: J
authors: Jura
authors: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
authors: Hanna
authors: H
authors: Rokita
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C000612068:MIRN3163 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; D002794:Choline
keywords: EXPRESSION MICROARRAYS; MONOCYTE CHEMOATTRACTANT PROTEIN-INDUCED PROTEIN 1 (ZC3H12A); NEUROBLASTOMA; PIN DOMAIN; microRNA