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原癌基因启动子甲基化导致鼻咽癌中原钙黏蛋白 17 表达降低。

Aberrant promoter methylation reduced the expression of protocadherin 17 in nasopharyngeal cancer.

机构信息

Department of Otolaryngology - Head and Neck Surgery, Clinical Division of Surgery, Chinese PLA General Hospital, Beijing, China, 100853.

出版信息

Biochem Cell Biol. 2019 Aug;97(4):364-368. doi: 10.1139/bcb-2017-0343. Epub 2018 Aug 30.

DOI:10.1139/bcb-2017-0343
PMID:30165032
Abstract

This study aimed to explore the underlying mechanism of protocadherin 17 (PCDH17) downregulated in nasopharyngeal cancer (NPC). NPC tumor and adjacent tissue samples were collected from NPC patients who received therapy in the Chinese PLA General Hospital. Meanwhile, a normal epithelial cell lines NP96 and 6 NPC and cell lines C666-1, CEN1, CEN2, HNE1, HEN2, and HONE1 were prepared. Then, the expression level of PCDH17 and the methylation level of PCDH17 promoter in both tissues samples and cell lines were determined using the PCR method. Moreover, PCDH17 was overexpressed in CNE2 and HONE1 using Lipo2000. Following this, the proliferation and apoptosis of CNE2 and HONE1 were assessed using MTT and flow cytometry. The expression of PCDH17 was significantly downregulated in NPC tissues compared with the adjacent tissues as well as in the NPC cell lines compared with the normal NP96 cells. Overexpressed PCDH17 could significantly inhibit the proliferation of CNE2 and HONE1 cells but obviously promote the apoptosis of these two cell lines. Aberrant hypermethylation in the promoter might be the explanation of PCDH17 downregulated in PCDH17 and promoted the development of NPC.

摘要

本研究旨在探讨鼻咽癌(NPC)中下调的原钙黏蛋白 17(PCDH17)的潜在机制。从在中国人民解放军总医院接受治疗的 NPC 患者中收集 NPC 肿瘤和相邻组织样本。同时,准备了正常上皮细胞系 NP96 和 6 个 NPC 细胞系 C666-1、CEN1、CEN2、HNE1、HEN2 和 HONE1。然后,使用 PCR 法测定组织样本和细胞系中 PCDH17 的表达水平和 PCDH17 启动子的甲基化水平。然后,使用 Lipo2000 在 CNE2 和 HONE1 中转染 PCDH17。接下来,使用 MTT 和流式细胞术评估 CNE2 和 HONE1 的增殖和凋亡。与相邻组织相比,NPC 组织中 PCDH17 的表达明显下调,与正常 NP96 细胞相比,NPC 细胞系中 PCDH17 的表达也下调。过表达 PCDH17 可明显抑制 CNE2 和 HONE1 细胞的增殖,但明显促进这两种细胞系的凋亡。启动子的异常高甲基化可能是 PCDH17 下调并促进 NPC 发展的原因。

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Protocadherin 17 is a tumor suppressor and is frequently methylated in nasopharyngeal carcinoma.
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Cancer Manag Res. 2019 Feb 18;11:1601-1613. doi: 10.2147/CMAR.S191102. eCollection 2019.