鼻咽癌細胞MeDIP-Seq測序reads在染色體上分布差異的研究

林偉達　王冬輝　羅海丹，3　蘇箔金　趙存友　楊惠玲★

鼻咽癌細胞MeDIP-Seq測序reads在染色體上分布差異的研究

林偉達1，2，3王冬輝1羅海丹1，3蘇箔金1趙存友4楊惠玲1★

［摘要］目的探討同源不同輻射抗拒鼻咽癌（nasopharyngeal carcinoma，NPC）細胞DNA甲基化差異，期望從表觀遺傳學角度闡述人鼻咽癌輻射抗拒的發生機制。方法采用MeDIP-Seq測序法對CNE2R／CNE2細胞進行測序，分析比較DNA甲基化水平差異區間的分布。結果CNE-2R和CNE-2細胞甲基化分布差異主要集中在第5、6、7、9、13、17號染色體上，其中第5、6、13、17號染色體上為甲基化上調區間的密集區域，第7、9號染色體上為甲基化下調的密集區域。結論同源不同輻射抗拒鼻咽癌細胞CNE-2R和CNE-2細胞的甲基化水平存在差異；差異甲基化水平可能與輻射抗拒相關。

［關鍵詞］鼻咽癌；甲基化；輻射抗拒

作者單位：1．中山大學中山醫學院病理生理學教研室，廣東，廣州510080 2．中山大學附屬第六醫院胃腸研究所，廣東，廣州510655 3．中山大學中山醫學院臨床醫學五年制，廣東，廣州510080 4．南方醫科大學基礎醫學院醫學遺傳學教研室，廣東，廣州510515

Research on different distributions of MeDIP-Seq reads in chromosomes of nasopharyngeal carcinoma cells

LIN Weida1,2,3, WANG Donghui1, LUO Haidan1,3, SU Bojin1, ZHAO Cunyou4, YANG Huiling1★
(1. Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China, 510080; 2. Gastrointestinal Institute, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China, 510655; 3. Clinical Medicine of Five-year Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China, 510080; 4. Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China, 510515)

[ABSTRACT] Objective To expound the pathogenetic mechanism of radiation resistance of NPC from an epigenetics perspective by discussing the differences of the DNA methylation levels of nasopharyngeal carcinoma (NPC) cells in the same genetic background but different radiation resistances. Methods MeDIP-Seq was performed to sequence the CNE-2 and CNE-2R cells. The distribution of different intervals of DNA methylation level was analyzed to detect the association between the DNA methylation and radiation resistance.ResultsThe differences mostly centralized in 5, 6, 7, 9, 13 and 17 chromosomes, which were up-regulated in 5, 6, 13 and 17 chromosomes and down-regulated in 7 and 9 chromosomes, respectively. Conclusion The DNA methylation levels between NPC cells in the same genetic background but different radiation resistances(CNE-2 and CNE-2R cells) were quite different, indicating that DNA methylation may be associated with NPC radioresistance.

[KEY WORDS] Nasopharyngeal carcinoma; Methylation; Radiation-resistance

鼻咽癌（nasopharyngeal carcinoma，NPC）是源自于人鼻咽部上皮組織的惡性腫瘤，為我國最常見的頭頸部惡性腫瘤之一［1］。目前放療仍為NPC首選療法，但由于放療過程中輻射抗拒的產生，嚴重制約NPC病人5年生存率的提高［2］。DNA甲基化是研究最早且較深入的表觀遺傳學標志之一，其介導的表觀遺傳學調控在腫瘤發生、發展和腫瘤治療中起了重要作用。已有研究報道DNA甲基化能夠影響腫瘤的放化療敏感性，如Kim等發現SERPINB5和S100A6基因CpG島的高甲基化能降低基因的表達，從而增加非小細胞肺癌的輻射抗拒［3］；……