title: Protein tyrosine phosphatase PTPRJ is negatively regulated by microRNA-328.
abstract: Expression of PTPRJ, which is a ubiquitous receptor-type protein tyrosine phosphatase, is significantly reduced in a vast majority of human epithelial cancers and cancer cell lines (i.e. colon, lung, thyroid, mammary and pancreatic tumours). A possible role for microRNAs (miRNAs) in the negative regulation of PTPRJ expression has never been investigated. In this study, we show that overexpression of microRNA-328 (miR-328) decreases PTPRJ expression in HeLa and SKBr3 cells. Further investigations demonstrate that miR-328 acts directly on the 3'UTR of PTPRJ, resulting in reduced mRNA levels. Luciferase assay and site-specific mutagenesis were used to identify a functional miRNA response element in the 3'UTR of PTPRJ. Expression of miR-328 significantly enhances cell proliferation in HeLa and SKBr3 cells, similar to the effects of downregulation of PTPRJ with small interfering RNA. Additionally, in HeLa cells, the proliferative effect of miR-328 was not observed when PTPRJ was silenced with small interfering RNA; conversely, restoration of PTPRJ expression in miR-328-overexpressing cells abolished the proliferative activity of miR-328. In conclusion, we report the identification of miR-328 as an important player in the regulation of PTPRJ expression, and we propose that the interaction of miR-328 with PTPRJ is responsible for miR-328-dependent increase of epithelial cell proliferation.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Catanzaro, Italy. francesco.paduano@unicz.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Paduano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dattilo
authors.forename: Domenico
authors.initials: D
authors.lastname: Narciso
authors.forename: Anna
authors.initials: A
authors.lastname: Bilotta
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.forename: Miranda
authors.initials: M
authors.lastname: Menniti
authors.forename: Valter
authors.initials: V
authors.lastname: Agosti
authors.forename: Camillo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Nicola
authors.initials: N
authors.lastname: Perrotti
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fusco
authors.forename: Francesco
authors.initials: F
authors.lastname: Trapasso
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Iuliano
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000704:Analysis of Variance; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D034622:RNA Interference; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3