TAp63-Regulated miRNAs Suppress Cutaneous Squamous Cell Carcinoma through Inhibition of a Network of Cell-Cycle Genes.

ABSTRACT: TAp63 is a p53 family member and potent tumor and metastasis suppressor. Here, we show that TAp63^-/- mice exhibit an increased susceptibility to ultraviolet radiation-induced cutaneous squamous cell carcinoma (cuSCC). A human-to-mouse comparison of cuSCC tumors identified miR-30c-2* and miR-497 as underexpressed in TAp63-deficient cuSCC. Reintroduction of these miRNAs significantly inhibited the growth of cuSCC cell lines and tumors. Proteomic profiling of cells expressing either miRNA showed downregulation of cell-cycle progression and mitosis-associated proteins. A mouse to human and cross-platform comparison of RNA-sequencing and proteomics data identified a 7-gene signature, including AURKA, KIF18B, PKMYT1, and ORC1, which were overexpressed in cuSCC. Kn

SUBMITTER: Davis AJ 

PROVIDER: S-EPMC7299759 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature