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Title: Expression inactivation of SMARCA4 by microRNAs in lung tumors
Authors: Isabel F. Coira
Eva E. Rufino-Palomares
Octavio A. Romero
Paola Peinado
Chanatip Metheetrairut
Laura Boyero-Corral
Julian Carretero
Esther Farez-Vidal
Marta Cuadros
Fernando J. Reyes-Zurita
Jose A. Lupiáñez
Montse Sánchez-Cespedes
Frank J. Slack
Pedro P. Medina
Universidad de Granada
Centre for Genomics and Oncological Research (GENYO)
Institut d'Investigacio Biomedica de Bellvitge
Yale University
University of Valencia
Mahidol University
Harvard Medical School
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2015
Citation: Human Molecular Genetics. Vol.24, No.5 (2015), 1400-1409
Abstract: © The Author 2014. SMARCA4 is the catalytic subunit of the SWI/SNF chromatin-remodeling complex, which alters the interactions between DNA and histones and modifies the availability of the DNA for transcription. The latest deep sequencing of tumor genomes has reinforced the important and ubiquitous tumor suppressor role of the SWI/SNF complex in cancer. However, although SWI/SNF complex plays a key role in gene expression, the regulation of this complex itself is poorly understood. Significantly, an understanding of the regulation of SMARCA4 expression has gained in importance due to recent proposals incorporating it in therapeutic strategies that use synthetic lethal interactions between SMARCA4-MAX and SMARCA4-SMARCA2. In this report,we found that the loss of expression of SMARCA4 observed in some primary lung tumors, whose mechanismwas largely unknown, can be explained, at least partially by the activity of microRNAs (miRNAs). We reveal that SMARCA4 expression is regulated by miR-101, miR-199 and especially miR-155 through their binding to two alternative 30UTRs. Importantly, our experiments suggest that the oncogenic properties of miR-155 in lung cancer can be largely explained by its role inhibiting SMARCA4. This new discovered functional relationship could explain the poor prognosis displayed by patients that independently have high miR-155 and lowSMARCA4 expression levels. In addition, these results could lead to application of incipient miRNA technology to the aforementioned synthetic lethal therapeutic strategies.
ISSN: 14602083
Appears in Collections:Scopus 2011-2015

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