Resistance to tumorigenesis in the african spiny mouse (Acomys) correlates with upregulation of multiple tumor suppressor genes

Abstract

Abstract Cancer remains a leading cause of morbidity and mortality worldwide, and the relationship between cancer and regeneration remains poorly understood. The spiny mouse ( Acomys sp . ) has attracted considerable attention due to its regenerative abilities. In this study, we compared the response of Mus musculus (C57/BL6) and Acomys dimidiatus mice to the DMBA/TPA papilloma inducing protocol. While both Mus and Acomys underwent DNA double strand breaks in their skin cells, mounted proliferative responses and underwent immune cell infiltration, only Mus developed tumors, whereas Acomys remained tumor-free. As an initial exploration of the molecular mechanisms underlying this resistance, we performed RNA sequencing on tissue samples from both species at baseline and at multiple time points during the carcinogenesis protocol. The data suggests distinctly different transcriptional responses between both species. Acomys showed significant upregulation of immune related genes, including a set of tumor suppressor genes, while Mus seemed to focus its response on modifying epidermis structure and regulation of the cell cycle.