期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14053
关键词
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资金
- Young Teachers Cultivation Project of Sun Yat-sen University from the Fundamental Research Funds for the Central Universities [16ykpy21]
- National Natural Science Foundation of China [81572658]
- Science and Technology Project of Guangzhou City, China [14570006]
- Health and Medical Collaborative Innovation Project of Guangzhou City, China [201400000001]
- Planned Science and Technology project of Guangdong Province [2013B020400004]
- National Science and Technology Pillar Program during the Twelfth Five-year Plan Period [2014BAI09B10]
Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment.
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