HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma.
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.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.|Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road west, Guangzhou, Guangdong 510055, China.
Xianyue
X
Ren
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Xiaojing
X
Yang
Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuan Road west, Guangzhou, Guangdong 510055, China.
Bin
B
Cheng
Department of Radiation Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang 310022, China.
Xiaozhong
X
Chen
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou, Guangdong 510006, China.
Tianpeng
T
Zhang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Qingmei
Q
He
Department of Radiation Oncology, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou, Zhejiang 310022, China.
Bin
B
Li
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Yingqin
Y
Li
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Xinran
X
Tang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Xin
X
Wen
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Qian
Q
Zhong
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Tiebang
T
Kang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Musheng
M
Zeng
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Na
N
Liu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China.
Jun
J
Ma
D000107:Acetylation; D000818:Animals; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C476884:HOPX protein, human; D006657:Histones; D018398:Homeodomain Proteins; D000071250:Snail Family Transcription Factors; D025521:Tumor Suppressor Proteins