TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.

Abstract

BACKGROUND:

Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown.

METHODS:

Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells.

RESULTS:

We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way.

CONCLUSIONS:

TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC.

• Authors: Xian-Yue Ren, Xin Wen, Ying-Qing Li, Jian Zhang, Qing-Mei He, Xiao-Jing Yang, Xin-Ran Tang, Ya-Qin Wang, Pan-Pan Zhang, Xiao-Zhong Chen, Bin Cheng, Jun Ma, Na Liu
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 37 Issue 1 Pg. 227 (Sep 14 2018) ISSN: 1756-9966 [Electronic] England
• PMID: 30217224 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Intracellular Signaling Peptides and Proteins
• TNFAIP8L3 protein, human

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Carcinoma (epidemiology, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• CpG Islands (genetics)
• DNA Methylation (genetics)
• Disease Progression
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (epidemiology, genetics, pathology)
• Neoplasm Metastasis
• Prognosis
• Xenograft Model Antitumor Assays