Prostate-specific CRISPR knock-in of human SKP2 induces prostatic intraepithelial neoplasia and adenocarcinoma and reprograms prostate microenvironment.

We therefore have established a prostate specific CRISPR human SKP2 (hSKP2) knock-in mouse model for studying its role in prostate carcinogenesis. Overexpression of hSKP2 which is driven by endogenous mouse probasin promoter induces prostatic lesions including hyperplasia, mouse prostate intraepithelial neoplasia (mPIN), and low-grade carcinoma and increase prostate weights.

Transcriptional profiling by RNA-sequencing analysis revealed significant gene expression alterations in epithelial to mesenchymal transition (EMT), extracellular matrix and interferon signaling in the prostate of hSKP2 knock-in mice compared to wild-type mice. Single cell deconvolution showed an increase of fibroblasts population and a decrease of CD8+T cell and B cell populations in the prostates of hSKP2-knock-in mice.