Zhang Ting, Qian Hua, Hu Cui, Lu Hui, Li Ji-Bing, Wu Ya-Fen, Li Wei
Cell Physiol Biochem. 2017;43(3):1188-1197. doi: 10.1159/000481759. Epub 2017 Oct 5.
BACKGROUND/AIMS: Ultraviolet B (UVB) damage is the most essential etiological factor in skin carcinogenesis, and apoptosis leads to the efficient elimination of UVB-damaged cells. However, the mechanisms underlying resistance to UVB-induced apoptosis remain unclear.
HaCaT and A431 cells were used in the present study. Quantitative real-time PCR, single cell PCR, and western blotting were used to examine cancer-related gene expression at the mRNA and protein levels.
We report that miR-26a, which is upregulated upon UVB irradiation, promotes UVB-induced apoptosis in HaCaT cells by targeting the histone methyltransferase EZH2. Moreover, the UVB/miR-26a/EZH2 regulatory axis largely depends on the MYC expression level. Interestingly, treatment with EZH2 inhibitors significantly enhanced UVB-induced apoptosis.
miR-26a/EZH2 might be potential targets for skin cancer prevention and therapy.
背景/目的：紫外线B（UVB）损伤是皮肤癌发生过程中最关键的病因，而细胞凋亡可有效清除UVB损伤的细胞。然而，对UVB诱导的细胞凋亡产生抗性的潜在机制仍不清楚。
本研究使用了HaCaT和A431细胞。采用定量实时PCR、单细胞PCR和蛋白质印迹法检测癌症相关基因在mRNA和蛋白质水平的表达。
我们发现，UVB照射后上调的miR-26a通过靶向组蛋白甲基转移酶EZH2促进HaCaT细胞中UVB诱导的细胞凋亡。此外，UVB/miR-26a/EZH2调控轴很大程度上取决于MYC的表达水平。有趣的是，用EZH2抑制剂处理可显著增强UVB诱导的细胞凋亡。
miR-26a/EZH2可能是皮肤癌预防和治疗的潜在靶点。
