TRIM3 suppressed the tumorigenicity of melanoma cells by ubiquitinating YAP1

Tripartite motif-containing 3 (TRIM 3), as a vital member of TRIM family, has been receiving significant attention in Cancer research. This research aims to detect the effect and relevant molecular functions of TRIM3 in melanoma cells.GEPIA website and immunohistochemical analysis were performed to investigate TRIM3 level in melanoma samples. The growth ability, the mobility, and the Apoptosis of M14 and A375 cells were determined by biological experiments. qPCR and western blot assays were performed to evaluate the expression of key genes. The interaction between TRIM3 and YAP1 was verified by immunoprecipitation and ubiquitination assays.A reduction of TRIM3 was observed in melanoma samples, and the loss of TRIM3 strengthened the proliferation and mobility of M14 and A375 cells and diminished Apoptosis, and vice versa. TRIM3 expression only affected the protein level of YAP1, while YAP1 mRNA was not changed. Then, we demonstrated that TRIM3 directly interacted with YAP1, and TRIM3 reduced YAP1 stability by inducing ubiquitination modification. Finally, rescue assays showed that si-YAP1 treatment alleviated the effects of si-TRIM3 on melanoma cells.This study indicated that depletion of TRIM3 strengthened the proliferation and mobility of M14 and A375 cells, suppressed cell Apoptosis, but these phenomena were counteracted by YAP1 down-regulation.

Melanoma; TRIM3; Ubiquitination; YAP1.