Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth

Li, Q and O'Malley, ME and Bartlett, DL and Guo, ZS (2011) Homeobox gene Rhox5 is regulated by epigenetic mechanisms in cancer and stem cells and promotes cancer growth. Molecular Cancer, 10.

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Abstract

Background: Homeobox genes murine Rhox5 and human RHOXF1 are expressed in early embryonic stages and then mostly restricted to germline tissues in normal adult, yet they are aberrantly expressed in cancer cells in vitro and in vivo . Here we study the epigenetic regulation and potential functions of Rhox5 gene.Findings: In Rhox5 -silenced or extremely low expresser cells, we observed low levels of active histone epigenetic marks (H3ac, H4ac and H3K4me2) and high levels of repressive mark H3K9me2 along with DNA hypermethylation in the promoter. In Rhox5 low expresser cells, we typically observed modest levels of both active and repressive histone marks along with moderate DNA methylation. In Rhox5 highly expressed CT26 cancer cells, we observed DNA hypomethylation along with high levels of both active and repressive histone marks. Epigenetic drugs (retinoic acid and MS-275) induced F9 cell differentiation with enhanced Rhox5 expression and dynamic changes of epigenetic marks. Finally, Rhox5 knockdown by small hairpin RNA (shRNA) in CT26 colon cancer decreased cell proliferation and migration in vitro and tumor growth in vivo .Conclusions: Both DNA methylation and histone methylation/acetylation play key roles in modulating Rhox5 expression in various cell types. The stem cell-like "bivalent domain", an epigenetic feature originally identified in key differentiation genes within stem cells, exists in the Rhox5 gene promoter in not only embryonic stem cells but also cancer cells, cancer stem cells, and differentiated Sertoli cells. As Ras signaling-dependent Rhox5 expression promotes tumor growth, Rhox5 may be an ideal target for therapeutic intervention in cancer. © 2011 Li et al; licensee BioMed Central Ltd.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Li, Q O'Malley, ME Bartlett, DL dlb3@pitt.edu DLB3 Guo, ZS zsg2@pitt.edu ZSG2
Centers:	Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date:	24 May 2011
Date Type:	Publication
Journal or Publication Title:	Molecular Cancer
Volume:	10
DOI or Unique Handle:	10.1186/1476-4598-10-63
Schools and Programs:	School of Medicine > Surgery
Refereed:	Yes
Date Deposited:	28 Oct 2016 18:48
Last Modified:	26 Jan 2019 10:55
URI:	http://d-scholarship.pitt.edu/id/eprint/30059

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