甲基丙烯酸环氧丙酯诱导16HBE细胞恶性转化相关m^(6)A修饰异常mRNA的分析  

m^(6)A methylation of m RNAs in glycidyl methacrylate-induced malignant transformation of 16HBE cells

作　　者：王苗 王全凯[1,2] 李昕苇 马顺鹏 乌瀚宝栎尔 许建宁[1,2] WANG Miao;WANG Quankai;LI Xinwei;MA Shunpeng;WUHAN Baolier;XU Jianning(National Institute of Occupational Health and Poison Control,Chinese Center for Disease Control and Prevention,Beijing 100050;Key Laboratory of Chemical Safety and Health,Chinese Center for Disease Control and Prevention,Beijing 100050,China)

机构地区：[1]中国疾病预防控制中心职业卫生与中毒控制所,北京100050 [2]中国疾病预防控制中心化学污染与健康安全重点实验室,北京100050

出　　处：《癌变．畸变．突变》2021年第6期405-409,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(81673221)。

摘　　要：目的:检测甲基丙烯酸环氧丙酯(GMA)诱导16HBE细胞恶性转化相关m RNA的m^(6)A甲基化修饰水平,筛选出m^(6)A修饰的m RNA并进行功能注释。方法:GMA(8μg/m L)重复染毒16HBE细胞后,收集GMA染毒组和DMSO对照组的第30代细胞,采用高通量人类表观转录组芯片检测16HBE细胞恶性转化相关m RNA的m^(6)A修饰水平,应用Visual Studio Code软件进行m^(6)A修饰m RNA的筛选,并利用Omicshare工具对这些m RNA进行GO富集分析和KEGG通路分析。结果:与对照组细胞比较,GMA诱导的恶性转化16HBE细胞中m^(6)A修饰水平异常的m RNA共有454个,其中高甲基化水平m RNA 334个,低甲基化水平m RNA 120个;表达水平异常的m RNA共有434个,其中高表达m RNA 236个,低表达m RNA 198个。m^(6)A修饰的m RNA有45个,GO富集分析结果显示上述m RNA主要富集于SNAP受体活性、SNARE结合、SNARE复合体等生物学过程,KEGG通路分析主要富集于囊泡运输中的SNARE相互作用、非同源末端连接、苯丙氨酸代谢等通路。结论:m^(6)A修饰m RNA可能在GMA诱导16HBE恶性转化过程发挥重要作用。OBJECTIVE:To investigate m^(6)A methylation levels of m RNAs which are related to glycidylmethacrylate(GMA)-induced malignant transformation of 16 HBE cells and their functional roles.METHODS:After 16 HBE cells were repeatedly exposed to GMA(8μg/m L),the 30 th generation cells of GMA group andDMSO control group were collected.m^(6)A methylation levels of m RNAs which were related to 16 HBE malignanttransformation were detected by high-throughput human apparent transcriptome chip.The differentially m^(6)A-methylated m RNAs and differentially expressed m RNAs were screened by Visual Studio Code.The Omicsharetools were used for GO enrichment and KEGG pathway analyses of these m RNAs.RESULTS:A total of 454 lnc RNAs with differential m^(6)A methylation were identified in GMA-induced 16 HBE malignant transformedcells,including 334 which were hypermethylated m RNAs and 120 which were hypomethylated m RNAs(|FC|>2.0,P<0.05).There was a total of 434 differentially expressed m RNAs,among which 236 were up-regulatedand 198 were down-regulated(|FC|>2.0,P<0.05).There were 45 m^(6)A-methylated m RNAs.The GO analysesshowed that SNAP receptor activity,SNARE binding and SNARE complex were the main biological processes.KEGG pathway analyses showed that m^(6)A-methylated m RNAs were enriched in SNARE interactions in vesiculartransport,non-homologous end-joining,and phenylalanine metabolism.CONCLUSION:Our data indicate thatm^(6)A methylation played an important role in the process of GMA-induced 16 HBE malignant transformation.

关 键 词：N^(6)-甲基腺嘌呤 甲基丙烯酸环氧丙酯 高通量基因芯片 恶性转化细胞 

分 类 号：R730.2[医药卫生—肿瘤]