Loss of epidermal MCPIP1 is associated with aggressive squamous cell carcinoma

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 (Mcpip1eKO). Papillomas that developed in Mcpip1eKO 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.

Construction and validation of a prognostic model for tongue cancer based on three genes signature

“…Keratins are a large class of proteins produced by keratinocytes in the skin, hair, nails, and other cornified cells, and are closely related to the occurrence and development of SCC. [10][11][12][13] Studies have shown that KRT33B is significantly suppressed in low-grade gliomas and is associated with poor prognosis, [14] suggesting that this protein may be a marker for differentiation status, with high expression indicating better differentiation and prognosis. This is consistent with our results (Figure S1A, Supplemental Digital Content, http://links.lww.com/MD/K753 and Figure S2A, Supplemental Digital Content, http://links.lww.com/MD/ K754), where patients with low KRT33B expression had significantly worse outcomes than those with high expression.…”