miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma.
miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma.
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DOI：
10.1038/srep32921
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发表时间：
2016-09-08
影响因子：
4.6
通讯作者：
Guo Z
中科院分区：
文献类型：
--
作者：
Wang C;Wu J;Zhao Y;Guo Z
组蛋白甲基转移酶Set8通过其3‘端非编码区的结合部位受miR-502调控，参与肿瘤的发生发展。对食管鳞癌患者MIR502和Set8结合位点rs16917496进行单核苷酸多态性分析，多因素分析显示Set8C/C基因型与术后较长生存期独立相关(相对危险度2.250；95%可信区间1.041~4.857；p = 0.039)。此外，Set8C/C基因介导的Set8表达降低与ESCC的生存期延长有关。功能分析表明，Set8基因敲除后可抑制ESCC细胞的增殖，促进其凋亡。随后的实验还表明，Set8基因敲除可显著抑制ESCC细胞的迁移和侵袭。我们的结果提示，通过改变miR-502与Set8 3‘UTR之间的结合亲和力，至少部分由miR-502介导的Set8表达的改变，可以通过抑制ECSS细胞的增殖和侵袭，促进ECSS细胞的凋亡来改变ESCC的转归。我们的数据表明，Set8是ESCC治疗的新靶点。
The histone methyltransferase SET8, whose expression is regulated by miR-502 though the binding site in the 3′ UTR of SET8, implicated in cancer development. Single nucleotide polymorphism (SNP) of rs16917496 located in the miR-502 and SET8 binding site was analyzed in esophageal squamous cell carcinoma (ESCC) patients, the SET8 C/C genotype was independently associated with longer post-operative survival by multivariate analysis (relative risk, 2.250; 95% CI, 1.041–4.857; p = 0.039). Moreover, the reduced SET8 expression mediated by SET8 C/C genotype was associated with longer ESCC survival. Functional assay indicated that the SET8 knock down could inhibit proliferation and promote apoptosis of ESCC cells. The subsequent assay also showed the markedly inhibition of ESCC cell migration and invasion by SET8 knock down. Our data suggested that the altering SET8 expression, which is mediated at least partly by miR-502 through changing the binding affinity between miR-502 and SET8 3′ UTR, could modify the ESCC outcome by inhibiting the proliferation and invasion as well as promoting the apoptosis of ECSS cell. Our data indicated that SET8 was a new target for ESCC therapy.
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