Universität zu Köln

Hufbauer, Martin, Lazic, Daliborka, Reinartz, Markus, Akguel, Baki, Pfister, Herbert and Weissenborn, Soenke Jan (2011). Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets. J. Dermatol. Sci., 64 (1). S. 7 - 16. CLARE: ELSEVIER IRELAND LTD. ISSN 1873-569X

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Abstract

Background: Dysregulation of microRNA(miRNA) expression is regularly found in various types of cancer and contributes to tumorigenic processes. However, little is known about miRNA expression in non-melanoma skin cancer in which a pathogenic role of beta human papillomaviruses (HPV) is discussed. A carcinogenic potential of beta HPV8 could be demonstrated in a transgenic mouse model, expressing all early genes of HPV8 (HPV8-CER). A single UVA/B-dose induced oncogene expression and led to papilloma growth within three weeks. Objective: Expression of miRNAs and their targets during HPV8-mediated tumor formation in mice. Methods: Skin of untreated or UV-irradiated wild-type and HPV8-CER mice was analyzed for miRNA expression and localization by qPCR and in situ hybridization. MiRNA target protein expression was analyzed by immunohistochemical staining. Results: Early steps in skin tumor formation in HPV8-CER mice were associated with an upregulation of the oncogenic miRNA-17-5p, -21 and -106a and a downregulation of the tumor-suppressive miRNA-155 and -206, which could be demonstrated by qPCR and in situ hybridization. The respective targets of miRNA-21 and -106a, the tumor suppressors PTEN, PDCD4 and Rb with their pivotal role in cell cycle regulation, apoptosis and proliferation were found to be downregulated. Conclusion: This is the first report demonstrating that a cutaneous HPV type deregulates the expression of miRNAs. These deregulations are closely related to the UV-induced upregulation of HPV8 oncogene levels, which suggest a direct or indirect HPV8-specific effect on miRNA expression. These data presume that HPV8 interferes with the miRNA mediated gene regulation to induce tumorigenesis. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hufbauer, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Lazic, Daliborka UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinartz, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Akguel, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Weissenborn, Soenke Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488162
DOI:	10.1016/j.jdermsci.2011.06.008
Journal or Publication Title:	J. Dermatol. Sci.
Volume:	64
Number:	1
Page Range:	S. 7 - 16
Date:	2011
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1873-569X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPIDERMODYSPLASIA-VERRUCIFORMIS; MICRORNA EXPRESSION; DOWN-REGULATION; EARLY GENES; CELL-CYCLE; CANCER; CLUSTER; PDCD4; PTEN; HPV Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48816