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Journal of Experimental & Clinical Cancer Research

Published in:

Open Access 01-12-2021 | Skin Cancer | Research

Loss of epidermal MCPIP1 is associated with aggressive squamous cell carcinoma

Authors: Weronika Szukala, Agata Lichawska-Cieslar, Roza Pietrzycka, Maria Kulecka, Izabela Rumienczyk, Michal Mikula, Iwona Chlebicka, Piotr Konieczny, Katarzyna Dziedzic, Jacek C Szepietowski, Giulia Fontemaggi, Janusz Rys, Jolanta Jura

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Squamous cell carcinoma (SCC) of the skin is a common form of nonmelanoma skin cancer. Monocyte chemotactic protein 1-induced protein 1 (MCPIP1), also called Regnase-1, is an RNase with anti-inflammatory properties. In normal human skin, its expression is predominantly restricted to the suprabasal epidermis. The main aim of this study was to investigate whether MCPIP1 is involved in the pathogenesis of SCC.

Methods

We analyzed the distribution of MCPIP1 in skin biopsies of patients with actinic keratoses (AKs) and SCCs. To explore the mechanisms by which MCPIP1 may modulate tumorigenesis in vivo, we established a mouse model of chemically induced carcinogenesis.

Results

Skin expression of MCPIP1 changed during the transformation of precancerous lesions into cutaneous SCC. MCPIP1 immunoreactivity was high in the thickened area of the AK epidermis but was predominantly restricted to keratin pearls in fully developed SCC lesions. Accelerated development of chemically induced skin tumors was observed in mice with loss of epidermal MCPIP1 (Mcpip1^eKO). Papillomas that developed in Mcpip1^eKO mouse skin were larger and characterized by elevated expression of markers typical of keratinocyte proliferation and tumor angiogenesis. This phenotype was correlated with enhanced expression of IL-6, IL-33 and transforming growth factor-beta (TGF-β). Moreover, our results demonstrated that in keratinocytes, the RNase MCPIP1 is essential for the negative regulation of genes encoding SCC antigens and matrix metallopeptidase 9.

Conclusions

Overall, our results provide a mechanistic understanding of how MCPIP1 contributes to the development of epidermoid carcinoma.

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Title: Loss of epidermal MCPIP1 is associated with aggressive squamous cell carcinoma
Authors: Weronika Szukala
Agata Lichawska-Cieslar
Roza Pietrzycka
Maria Kulecka
Izabela Rumienczyk
Michal Mikula
Iwona Chlebicka
Piotr Konieczny
Katarzyna Dziedzic
Jacek C Szepietowski
Giulia Fontemaggi
Janusz Rys
Jolanta Jura
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Skin Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02202-3

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