Oncotarget

Research Papers:

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

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 and Zhe Zhang _

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Oncotarget. 2015; 6:41077-41091. https://doi.org/10.18632/oncotarget.6218

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Abstract

Xiaoying Zhou1,2,*, Jiazhang Wei1,*, Fu Chen3, Xue Xiao1, Tingting Huang1, Qian He1, Shumin Wang1, Chunping Du1, Yingxi Mo1,4, Longde Lin5, Ying Xie1, Lili Wei1, Ying Lan1, Mairiko Murata4, Guangwu Huang1, Ingemar Ernberg2, Liudmila Matskova2, Zhe Zhang1

1Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Guangxi, China

2Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden

3Department of Radiation Oncology, Eye Ear Nose & Throat Hospital of Fudan University, Shanghai, China

4Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie, Japan

5School of Public Health, Guangxi Medical University, Guangxi, China

*These authors have contributed equally to this work

Correspondence to:

Ingemar Ernberg e-mail: [email protected]

Zhe Zhang e-mail: [email protected]

Keywords: UBE2L6, nasopharyngeal carcinoma, DNA methylation, tumor suppressor gene, ATGL

Received: April 30, 2015     Accepted: August 20, 2015     Published: October 12, 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.


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