title: Elevated expression of Rad18 regulates melanoma cell proliferation.
abstract: The E3 ligase Rad18 is a key regulator for the lesion bypass pathway, which plays an important role in genomic stability. However, the status of Rad18 expression in melanoma is not known. Using melanoma tissue microarray (TMA), we showed that nuclear Rad18 expression was upregulated in primary and metastatic melanoma compared to dysplastic nevi. Rad18 expression was significantly reduced in sun-exposed sites compared to the sun-protected sites. Strong Rad18 expression correlated with worse 5-year patient survival and was an independent prognostic factor for melanoma found in the sun-protected sites. Furthermore, we showed that melanoma cell proliferation and the expression of pAkt and cyclin D1 were reduced upon Rad18 knockdown. We, for the first time, showed that Rad18 is significantly increased in melanoma and predicts the poor outcome for melanoma in the sun-protected sites. Rad18 is involved in the regulation of melanoma cell proliferation, which can be exploited in designing new strategy for melanoma treatment.
authors.affiliation: Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ronald P C
authors.initials: RP
authors.lastname: Wong
authors.forename: Almass-houd
authors.initials: AH
authors.lastname: Aguissa-Touré
authors.forename: Aijaz A
authors.initials: AA
authors.lastname: Wani
authors.forename: Shahram
authors.initials: S
authors.lastname: Khosravi
authors.forename: Michal
authors.initials: M
authors.lastname: Martinka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D016019:Survival Analysis; D044767:Ubiquitin-Protein Ligases
chemical_list: C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; C485954:RAD18 protein, human; D019938:Cyclin D1; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt