Nuclear Receptor Coactivator NCOA3 Regulates UV Radiation-Induced DNA Damage and Melanoma Susceptibility.

ABSTRACT: Melanoma occurs as a consequence of inherited susceptibility to the disease and exposure to UV radiation (UVR) and is characterized by uncontrolled cellular proliferation and a high mutational load. The precise mechanisms by which UVR contributes to the development of melanoma remain poorly understood. Here we show that activation of nuclear receptor coactivator 3 (NCOA3) promotes melanomagenesis through regulation of UVR sensitivity, cell-cycle progression, and circumvention of the DNA damage response (DDR). Downregulation of NCOA3 expression, either by genetic silencing or small-molecule inhibition, significantly suppressed melanoma proliferation in melanoma cell lines and patient-derived xenografts. NCOA3 silencing suppressed expression of xeroderma pigmentosum C and increased melanoma

SUBMITTER: de Semir D 

PROVIDER: S-EPMC8178194 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature