Palmitoyl acyltransferase ZDHHC7 suppresses prostate cancer through inhibiting androgen receptor expression

We examined ZDHHC family gene expression in human tissue collection and identified ZDHHC7 as a PCa-relevant member. RNA-seq analyses of PCa cells with ZDHHC7 de-regulation revealed global alterations in androgen response and cell cycle pathways. Mechanistically, ZDHHC7 inhibits AR gene transcription and therefore reduces AR protein levels and abolishes AR signaling in PCa cells. Accordingly, ZDHHC7 depletion increased oncogenic properties of PCa cells, whereas restoring ZDHHC7 is sufficient to suppress PCa cell proliferation and invasion in vitro and mitigate xenograft tumor growth in vivo. Lastly, we demonstrated that ZDHHC7 is down-regulated in human PCa compared to benign adjacent tissues and its loss is associated with worse clinical outcomes. Taken together, our findings unequivocally prove ZDHHC7 as a tumor suppressor gene that inhibits AR signaling and PCa progression, identifying ZDHHC7 loss as a biomarker for aggressive PCa and a target for therapeutic intervention. Overall design: RNA-seq of prostate cancer cells with ZDHHC7 overexpression or knockdown