Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma.
Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma.
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DOI：
10.18632/oncotarget.6218
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Zhang Z
中科院分区：
文献类型：
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作者：
Zhou X;Wei J;Chen F;Xiao X;Huang T;He Q;Wang S;Du C;Mo Y;Lin L;Xie Y;Wei L;Lan Y;Murata M;Huang G;Ernberg I;Matskova L;Zhang Z
我们确定了UBE 2L 6基因，编码ISG 15结合酶UbcH 8，作为一个基因显着下调启动子甲基化在鼻咽癌（NPC）。UbcH 8蛋白表达降低与NPC患者预后不良相关。UBE 2L 6的恢复表达抑制NPC细胞的增殖和集落形成，同时诱导细胞凋亡。特别令人感兴趣的是，我们发现，异常脂质周转控制UbcH 8在NPC通过ISG 15结合的valosin-containing蛋白（VCP）。与对照鼻咽上皮和非癌细胞系相比，肿瘤组织和NPC细胞系显示出明显强的脂滴（LD）积聚。我们证明，UbcH 8抵消脂肪细胞甘油三酯脂肪酶（ATGL），在脂质催化剂的关键酶的降解。
We identified the UBE2L6 gene, encoding the ISG15-conjugating enzyme UbcH8, as one gene significantly downregulated by promoter hypermethylation in nasopharyngeal carcinoma (NPC). Reduced expression of the UbcH8 protein correlated with poor outcome in NPC patients. Restored expression of UBE2L6 suppressed proliferation and colony formation in NPC cells, while inducing apoptosis. Of particular interest, we found that aberrant lipid turnover was controlled by UbcH8 in NPC through ISG15-conjugation of valosin-containing protein (VCP). Tumor tissue and NPC cell lines showed conspicuously strong accumulation of lipid droplets (LDs) compared to control nasopharyngeal epithelium and non-cancerous cell lines. We demonstrated that UbcH8 counteracts degradation of adipocyte triglyceride lipase (ATGL), a key enzyme in lipid catabolism.