Comparison of gene expression profiles reveals aberrant expression of FOXO1, Aurora A/B and EZH2 in lesional psoriatic skins
Psoriasis is a chronic, non-infectious skin disease affects 2–3% of the population worldwide. In order to find genes possibly cause this skin disease, we re-analyzed the gene expression data-sets from three published studies. We compared the gene expression profiles between lesional psoriatic skin (PP), uninvolved psoriatic skin (PN) and normal skin (NN) tissues. We found that compared with in PN and NN tissues, the expression of FOXO1 is significantly repressed and the expression of AURKA, AURKB and EZH2 is significantly up-regulated in PP tissues (P < 0.001). During the treatment of psoriasis patients with TNF-α antagonist Etanercept, the expression of FOXO1 was re-activated and the expression of AURKA and EZH2 was repressed. These results suggest loss of FOXO1 expression and elevated AURKA/B and EZH2 expression in lesional psoriatic tissues have potential contribution to the development of psoriasis. It is worthwhile to test whether the combination of Aurora kinases or EZH2 inhibitors can enhance the therapeutic effects of Etanercept in psoriasis management.
KeywordsPsoriasis Microarray FOXO1 Aurora kinases EZH2 Etanercept
- 8.Zaba LC, Suárez-Fariñas M, Fuentes-Duculan J, Nograles KE, Guttman-Yassky E, Cardinale I, Lowes MA, Krueger JG (2009) Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 124:1022–1030PubMedCrossRefGoogle Scholar
- 26.Menter A, Gottlieb A, Feldman SR, Van Voorhees AS, Leonardi CL, Gordon KB, Lebwohl M, Koo JY, Elmets CA, Korman NJ, Beutner KR, Bhushan R (2008) Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 58:826–850PubMedCrossRefGoogle Scholar
- 27.Gottlieb A, Korman NJ, Gordon KB, Feldman SR, Lebwohl M, Koo JY, Van Voorhees AS, Elmets CA, Leonardi CL, Beutner KR, Bhushan R, Menter A (2008) Guidelines of care for the management of psoriasis and psoriatic arthritis: section 2. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol 58:851–864PubMedCrossRefGoogle Scholar
- 28.Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM (2004) VX-680, a potent and selective small-molecule inhibitor of the aurora kinases, suppresses tumor growth in vivo. Nat Med 10:262–267PubMedCrossRefGoogle Scholar