CBX7 and HMGA1b proteins act in opposite way on the regulation of the SPP1 gene expression

CBX7 and HMGA1b proteins act in opposite way on the regulation of the SPP1 gene expression

Author Sepe, Romina Google Scholar
Formisano, Umberto Google Scholar
Federico, Antonella Google Scholar
Forzati, Floriana Google Scholar
Bastos, Andre Uchimura Autor UNIFESP Google Scholar
D'Angelo, Daniela Google Scholar
Cacciola, Nunzio Antonio Google Scholar
Fusco, Alfredo Google Scholar
Pallante, Pierlorenzo Google Scholar
Institution Univ Naples Federico II
Universidade Federal de São Paulo (UNIFESP)
Inst Nacl Canc INCA
Abstract Several recent studies have reported the Polycomb Repressive Complex 1 member CBX7 as a tumor-suppressor gene whose expression progressively decreases in different human carcinomas in relation with tumor grade, malignant stage and poor prognosis. We have previously demonstrated that CBX7 is able to inhibit the expression of the SPP1 gene, encoding the chemokine osteopontin that is over-expressed in cancer and has a critical role in cancer progression.Here, we have analyzed the mechanism by which CBX7 regulates the SPP1 gene expression. We show that the SPP1 transcriptional regulation mechanism involves the CBX7-interacting protein HMGA1b, that acts as a positive regulator of the SPP1 gene. In fact, we demonstrate that, in contrast with the transcriptional activity of CBX7, HMGA1b is able to increase the SPP1 expression by inducing the activity of its promoter. Moreover, we show that CBX7 interferes with HMGA1b on the SPP1 promoter and counteracts the positive transcriptional activity of HMGA1b on the SPP1 expression.Furthermore, since we found that also the NF-kappa B complex resulted involved in the modulation of the SPP1 expression in thyroid cells, we suppose that CBX7/HMGA1b/NF-kappa B could take part in the same transcriptional mechanism that finally leads to the regulation of the SPP1 gene expression.Taken together, our data show the important role played by CBX7 in the negative regulation of the SPP1 gene expression, thus contributing to prevent the acquisition of a malignant phenotype.
Keywords Osteopontin
CBX7
HMGA1b
NF-kappa B
thyroid carcinomas
Language English
Sponsor Associazione Italiana per la Ricerca sul Cancro-AIRC
Ministero dell'Istruzione, dell'Universita e della Ricerca MIUR
P.O.R. Campania FSE Progetto CREMe
Progetto di Interesse strategico Invecchiamento (PNR-CNR Aging Program) PNR-CNR
Progetto Nuove strategie nanotecnologiche per la messa a punto di farmaci e presidi diagnostici diretti verso cellule cancerose circolanti
CNR Epigenomics Flagship Project EPIGEN
CNR Nanomax Progetto Bandiera DESIRED
Grant number Associazione Italiana per la Ricerca sul Cancro-AIRC: IG 11477
Progetto Nuove strategie nanotecnologiche per la messa a punto di farmaci e presidi diagnostici diretti verso cellule cancerose circolanti: PON01-02782
Date 2015-02-20
Published in Oncotarget. Albany: Impact Journals Llc, v. 6, n. 5, p. 2680-2692, 2015.
ISSN 1949-2553 (Sherpa/Romeo, impact factor)
Publisher Impact Journals Llc
Extent 2680-2692
Origin http://dx.doi.org/10.18632/oncotarget.2777
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000352694400011
URI http://repositorio.unifesp.br/11600/45066

Show full item record




File

File Size Format View

There are no files associated with this item.

This item appears in the following Collection(s)

Search


Browse

Statistics

My Account