Protocadherin 17 is a tumor suppressor and is frequently methylated in nasopharyngeal carcinoma
Authors He Y, Wang Z, Liu C, Gong Z, Li Y, Lu T, Hu G
Received 16 October 2018
Accepted for publication 13 January 2019
Published 18 February 2019 Volume 2019:11 Pages 1601—1613
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Xueqiong Zhu
Ya He,1,2 Zhihai Wang,1 Chuan Liu,1 Zhitao Gong,1 Yanshi Li,1 Tao Lu,1 Guohua Hu1
1Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 2Department of Otolaryngology Head and Neck Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
Purpose: Several PCDH genes were shown to be downregulated or silenced in carcinomas and act as candidate tumor suppressor genes. However, the functions of PCDH17 in nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the PCDH17 promoter methylation status and its impact on the expression and functions of PCDH17 in NPC.
Patients and methods: To determine the mRNA levels and promoter methylation status of PCDH17 in NPC cell lines as well as 42 NPC patient specimens, we performed reverse transcription PCR, methylation-specific PCR, and bisulfite genome sequencing. The effects of ectopic PCDH17 expression in NPC cell lines were determined by colony formation, cell proliferation, wound healing, in vitro human umbilical vein endothelial cells tube formation, migration, invasion, cell cycle, and apoptosis assays and an in vivo subcutaneous tumor model.
Results: PCDH17 expression was almost absent or significantly reduced in 100% of the NPC cell lines (5/5). However, 5-aza-2′-deoxycytidine and trichostatin A treatment restored PCDH17 expression. Promoter methylation was involved in PCDH17 silencing. Ectopic expression of PCDH17 in silenced NPC cells reduced colony formation, cell migration, angiogenesis, VEGF secretion, and tumorigenicity.
Conclusion: PCDH17 plays a tumor suppressor role in NPC. PCDH17 methylation may be a tumor-specific event and can be used as an epigenetic biomarker for NPC.
Keywords: nasopharyngeal carcinoma, PCDH17, tumor suppressor gene, methylation, epigenetic inactivation
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