Abstract
Abstract
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.