Orouji Elias, Peitsch Wiebke K, Orouji Azadeh, Houben Roland, Utikal Jochen
Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany.
Cancers (Basel). 2020 Apr 24;12(4):1057. doi: 10.3390/cancers12041057.
Merkel cell carcinoma (MCC) is a deadly skin cancer, and about 80% of its cases have been shown to harbor integrated Merkel polyomavirus in the tumor cell genome. Viral oncoproteins expressed in the tumor cells are considered as the oncogenic factors of these virus-positive Merkel cell carcinoma (VP-MCC). In contrast, the molecular pathogenesis of virus-negative MCC (VN-MCC) is less well understood. Using gene expression analysis of MCC cell lines, we found histone methyltransferase PRDM8 to be elevated in VN-MCC. This finding was confirmed by immunohistochemical analysis of MCC tumors, revealing that increased PRDM8 expression in VN-MCC is also associated with increased H3K9 methylation. CRISPR-mediated silencing of PRDM8 in MCC cells further supported the histone methylating role of this protein in VN-MCC. We also identified miR-20a-5p as a negative regulator of PRDM8. Taken together, our findings provide insights into the role of PRDM8 as a histone methyltransferase in VN-MCC tumorigenesis.
默克尔细胞癌（MCC）是一种致命的皮肤癌，约80%的病例显示肿瘤细胞基因组中存在整合的默克尔多瘤病毒。肿瘤细胞中表达的病毒癌蛋白被认为是这些病毒阳性默克尔细胞癌（VP-MCC）的致癌因素。相比之下，病毒阴性MCC（VN-MCC）的分子发病机制尚不太清楚。通过对MCC细胞系进行基因表达分析，我们发现组蛋白甲基转移酶PRDM8在VN-MCC中表达上调。MCC肿瘤的免疫组织化学分析证实了这一发现，表明VN-MCC中PRDM8表达增加也与H3K9甲基化增加有关。CRISPR介导的MCC细胞中PRDM8沉默进一步支持了该蛋白在VN-MCC中的组蛋白甲基化作用。我们还确定miR-20a-5p是PRDM8的负调节因子。综上所述，我们的研究结果为PRDM8作为组蛋白甲基转移酶在VN-MCC肿瘤发生中的作用提供了见解。
