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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene

Authors: Floriana Forzati, Marco De Martino, Francesco Esposito, Romina Sepe, Simona Pellecchia, Umberto Malapelle, Gianluca Pellino, Claudio Arra, Alfredo Fusco

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Loss of CBX7 expression has been described in several malignant neoplasias, including human colon and thyroid carcinomas proposing CBX7 as a tumor suppressor gene with a key role in cancer progression. This role is supported from the development of benign and malignant neoplasias in Cbx7 null mice.
The aim of our work has been to investigate the mechanisms underlying the CBX7 oncosuppressor activity by analyzing the microRNAs (miRNAs) regulated by CBX7.

Methods

The miRNA expression profiles of the mouse embryonic fibroblasts (MEFs) null for Cbx7 and the wild-type counterpart were analyzed by the miRNACHIP microarray and then validated by qRT-PCR. To asses KRAS as target of miR-155 we evaluated the protein levels after transfection of the synthetic miR-155. Human colon carcinoma samples have been investigated for the expression of CBX7 and miR-155.

Results

Twenty miRNAs were found upregulated and nine, including miR-155, downregulated in cbx7-null MEFS in comparison with the wild-type ones. Then, we focused on miR-155 since several studies have shown its deregulated expression in several human malignancies and, moreover, was the most downregulated miRNA. Subsequently, we searched for miR-155 target genes demonstrating that KRAS protein levels are directly modulated by miR-155. A direct significant correlation (r = 0.6779) between CBX7 and miR-155 expression levels was found in a set of human colon carcinoma tissue samples.

Conclusion

miR-155 is positively regulated by CBX7 in MEFs and colon carcinomas, and has KRAS as one of the target genes likely accounting for the anti-apoptotic activity ascribed to miR-155 in some tissue contexts.
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Metadata
Title
miR-155 is positively regulated by CBX7 in mouse embryonic fibroblasts and colon carcinomas, and targets the KRAS oncogene
Authors
Floriana Forzati
Marco De Martino
Francesco Esposito
Romina Sepe
Simona Pellecchia
Umberto Malapelle
Gianluca Pellino
Claudio Arra
Alfredo Fusco
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3158-z

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