ZNF281/Zfp281 is a target of miR-1 and counteracts muscle differentiation.

Autor: Nicolai S; Medical Research Council, Toxicology Unit, Department of Pathology, University of Cambridge, UK., Pieraccioli M; Department of Experimental Medicine, University of Rome Tor Vergata, Italy., Smirnov A; Department of Experimental Medicine, University of Rome Tor Vergata, Italy., Pitolli C; Medical Research Council, Toxicology Unit, Department of Pathology, University of Cambridge, UK., Anemona L; Department of Experimental Medicine, University of Rome Tor Vergata, Italy., Mauriello A; Department of Experimental Medicine, University of Rome Tor Vergata, Italy., Candi E; Department of Experimental Medicine, University of Rome Tor Vergata, Italy.; Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy., Annicchiarico-Petruzzelli M; Istituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy., Shi Y; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.; The First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, Suzhou, China., Wang Y; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China., Melino G; Medical Research Council, Toxicology Unit, Department of Pathology, University of Cambridge, UK.; Department of Experimental Medicine, University of Rome Tor Vergata, Italy., Raschellà G; Laboratory of Health and Environment, ENEA, Rome, Italy.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2020 Feb; Vol. 14 (2), pp. 294-308. Date of Electronic Publication: 2019 Dec 24.
DOI: 10.1002/1878-0261.12605
Abstrakt: Defects in achieving a fully differentiated state and aberrant expression of genes and microRNAs (miRs) involved in differentiation are common to virtually all tumor types. Here, we demonstrate that the zinc finger transcription factor ZNF281/Zfp281 is down-regulated during epithelial, muscle, and granulocytic differentiation in vitro. The expression of this gene is absent in terminally differentiated human tissues, in contrast to the elevated expression in proliferating/differentiating ones. Analysis of the 3'UTR of ZNF281/Zfp281 revealed the presence of numerous previously undescribed miR binding sites that were proved to be functional for miR-mediated post-transcriptional regulation. Many of these miRs are involved in differentiation pathways of distinct cell lineages. Of interest, ZNF281/Zfp281 is able to inhibit muscle differentiation promoted by miR-1, of which ZNF281/Zfp281 is a direct target. These data suggest that down-regulation of ZNF281/Zfp281 during differentiation in various cell types may occur through specific miRs whose expression is tissue-restricted. In addition, we found that in rhabdomyosarcoma and leiomyosarcoma tumors, the expression of ZNF281/Zfp281 is significantly higher compared with normal counterparts. We extended our analysis to other human soft tissue sarcomas, in which the expression of ZNF281 is associated with a worse prognosis. In summary, we highlight here a new role of ZNF281/Zfp281 in counteracting muscle differentiation; its down-regulation is at least in part mediated by miR-1. The elevated expression of ZNF281/Zfp281 in soft tissue sarcomas warrants further analysis for its possible exploitation as a prognostic marker in this class of tumors.
(© 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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