Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma | Zendy

Xiaoying Zhou | Zendy; Jiazhang Wei | Zendy; Fu Chen | Zendy; Xue Xiao | Zendy; Tingting Huang | Zendy; Qian He | Zendy; Shumin Wang | Zendy; Chunping Du | Zendy; Yingxi Mo | Zendy; Longde Lin | Zendy; Ying Xie | Zendy; Lili Wei | Zendy; Ying Lan | Zendy; Mairiko Murata | Zendy; Guangwu Huang | Zendy; Ingemar Ernberg | Zendy; Liudmila Matskova | Zendy; Zhe Zhang | Zendy

Open Access

Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma

Author(s) -

Xiaoying Zhou,

Jiazhang Wei,

Fu Chen,

Xue Xiao,

Tingting Huang,

Qian He,

Shumin Wang,

Chunping Du,

Yingxi Mo,

Longde Lin,

Ying Xie,

Lili Wei,

Ying Lan,

Mairiko Murata,

Guangwu Huang,

Ingemar Ernberg,

Liudmila Matskova,

Zhe Zhang

Publication year - 2015

Publication title -

oncotarget

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.373

H-Index - 127

ISSN - 1949-2553

DOI - 10.18632/oncotarget.6218

Subject(s) - nasopharyngeal carcinoma , downregulation and upregulation , isg15 , cancer research , catabolism , cell culture , apoptosis , biology , cell growth , epigenetics , lipid droplet , lipolysis , enzyme , chemistry , endocrinology , medicine , microbiology and biotechnology , gene , biochemistry , adipose tissue , ubiquitin , genetics , radiation therapy

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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