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Identification of RNF4 dependent gene signature in melanoma tumors

ABSTRACT: Among hallmarks of cancer is impaired proteostasis, that is characterized by increased oncoprotein stability. Here we demonstrate that RNF4, a ubiquitin ligase implicated in the stabilization of short-lived oncoproteins, is important for melanoma tumorigenesis. High levels of RNF4 in melanoma patient-derived specimens coincide with poor prognosis. Accordingly, RNF4, is essential for the growth and migration and survival of melanoma cells, both in culture and in xenograft models. RNA-seq analyses of RNF4-expressing tumors identified a gene signature related to melanoma growth and migration. Among the upstream regulators of RNF4-dependent gene signature are c-Myc and HIF1a which exhibit elevated protein levels that also coincided with stabilization of the translation initiation regulator p-eIF2a. Correspondingly, the effects of RNF4 on melanomagenesis are p-eIF2a-dependent, thus highlighting an unexpected regulatory axis in melanoma via RNF4-and ubiquitin-dependent protein stabilization

ORGANISM(S): Homo sapiens

PROVIDER: GSE124064 | GEO | 2021/05/05

REPOSITORIES: GEO

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