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Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma.
- Source :
-
Oncotarget [Oncotarget] 2015 Dec 01; Vol. 6 (38), pp. 41077-91. - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Adenosine Triphosphatases genetics
Adenosine Triphosphatases metabolism
Apoptosis genetics
Azacitidine analogs & derivatives
Azacitidine pharmacology
Blotting, Western
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cell Line, Tumor
Cell Proliferation genetics
Cytokines genetics
Cytokines metabolism
DNA Methylation
Decitabine
Enzyme Inhibitors pharmacology
Gene Expression Profiling methods
Gene Expression Regulation, Neoplastic drug effects
HEK293 Cells
Humans
Kaplan-Meier Estimate
Lipase genetics
Lipase metabolism
Lipid Droplets metabolism
Nasopharyngeal Neoplasms metabolism
Nasopharyngeal Neoplasms pathology
Prognosis
Promoter Regions, Genetic
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Ubiquitin-Conjugating Enzymes metabolism
Ubiquitins genetics
Ubiquitins metabolism
Valosin Containing Protein
Down-Regulation
Epigenesis, Genetic
Lipolysis genetics
Nasopharyngeal Neoplasms genetics
Ubiquitin-Conjugating Enzymes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26506425
- Full Text :
- https://doi.org/10.18632/oncotarget.6218