Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Pigment Cell Melanoma Res. 2012 Mar;25(2):213-8. doi: 10.1111/j.1755-148X.2011.00948.x. Epub 2012 Jan 12.
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.
E3 连接酶 Rad18 是损伤旁路途径的关键调节因子，在基因组稳定性中发挥重要作用。然而，黑色素瘤中 Rad18 的表达状态尚不清楚。使用黑色素瘤组织微阵列（TMA），我们显示与发育不良痣相比，原发和转移性黑色素瘤中核 Rad18 表达上调。与避光部位相比，暴露于阳光的部位 Rad18 表达显著降低。强 Rad18 表达与更差的 5 年患者生存率相关，并且是在避光部位发现的黑色素瘤的独立预后因素。此外，我们还表明，Rad18 敲低可降低黑色素瘤细胞的增殖以及 pAkt 和细胞周期蛋白 D1 的表达。我们首次表明，Rad18 在黑色素瘤中显著增加，并预测避光部位黑色素瘤的不良预后。Rad18 参与调节黑色素瘤细胞的增殖，这可用于设计治疗黑色素瘤的新策略。
