The transcription factor p53 is a key player in the tumour suppressive DNA damage response and a growing number of target genes involved in these pathways has been identified. p53 has been shown to be implicated in controlling cell motility and its mutant form enhances metastasis by loss of cell directionality, but the p53 role in this context has not yet being investigated. Here, we report that ZNF185, an actin cytoskeleton-associated protein from LIM-family of Zn-finger proteins, is induced following DNA-damage. ChIP-seq analysis, chromatin crosslinking immune-precipitation experiments and luciferase assays demonstrate that ZNF185 is a bona fide p53 target gene. Upon genotoxic stress, caused by DNA-damaging drug etoposide and UVB irradiation, ZNF185 expression is up-regulated and in etoposide-treated cells, ZNF185 depletion does not affect cell proliferation and apoptosis, but interferes with actin cytoskeleton remodelling and cell polarization. Bioinformatic analysis of different types of epithelial cancers from both TCGA and GTEx databases showed a significant decrease in ZNF185 mRNA level compared to normal tissues. These findings are confirmed by tissue micro-array IHC staining. Our data highlight the involvement of ZNF185 and cytoskeleton changes in p53-mediated cellular response to genotoxic stress and indicate ZNF185 as potential biomarker for epithelial cancer diagnosis.
Keywords: DNA damage; ZNF185; cytoskeleton; epithelial cancer; p53; skin.