Journal
ONCOTARGET
Volume 6, Issue 38, Pages 41077-41091Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.6218
Keywords
UBE2L6; nasopharyngeal carcinoma; DNA methylation; tumor suppressor gene; ATGL
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Funding
- National Basic Research Program of China [2011CB504300, 2012CB526600]
- National Natural Foundation of China [81060167, 81272983]
- Swedish Cancer Society
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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.
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