Integrative analyses of N6‐methyladenosine‐associated single‐nucleotide polymorphisms (m6A‐SNPs) identify tumor suppressor gene AK9 in lung cancer

单核苷酸多态性 生物 肺癌 基因型 肺癌易感性 SNP公司 遗传学 基因 生物信息学 等位基因 癌症 表观遗传学 癌症研究 分子生物学 肿瘤科 医学
作者
Tingting Hua,Chang Zhang,Yating Fu,Na Qin,Su Liu,Congcong Chen,Linnan Gong,Huimin Ma,Yue Ding,Xiaoxia Wei,Chenying Jin,Jin Chen,Meng Zhu,Erbao Zhang,Juncheng Dai,Hongxia Ma
出处
期刊:Molecular Carcinogenesis [Wiley]
卷期号:63 (3): 538-548 被引量:2
标识
DOI:10.1002/mc.23669
摘要

Abstract N 6 ‐methyladenosine (m 6 A) modification has been identified as one of the most important epigenetic regulation mechanisms in the development of human cancers. However, the association between m 6 A‐associated single‐nucleotide polymorphisms (m 6 A‐SNPs) and lung cancer risk remains largely unknown. Here, we identified m 6 A‐SNPs and examined the association of these m 6 A‐SNPs with lung cancer risk in 13,793 lung cancer cases and 14,027 controls. In silico functional annotation was used to identify causal m 6 A‐SNPs and target genes. Furthermore, methylated RNA immunoprecipitation and quantitative real‐time polymerase chain reaction (MeRIP‐qPCR) assay was performed to assess the m 6 A modification level of different genotypes of the causal SNP. In vitro assays were performed to validate the potential role of the target gene in lung cancer. A total of 8794 m 6 A‐SNPs were detected, among which 397 SNPs in nine susceptibility loci were associated with lung cancer risk, including six novel loci. Bioinformatics analyses indicated that rs1321328 in 6q21 was located around the m 6 A modification site of AK9 and significantly reduced AK9 expression ( β = −0.15, p = 2.78 × 10 −8 ). Moreover, AK9 was significantly downregulated in lung cancer tissues than that in adjacent normal tissues of samples from the Cancer Genome Atlas and Nanjing Lung Cancer Cohort. MeRIP‐qPCR assay suggested that C allele of rs1321328 could significantly decrease the m 6 A modification level of AK9 compared with G allele. In vitro assays verified the tumor‐suppressing role of AK9 in lung cancer. These findings shed light on the pathogenic mechanism of lung cancer susceptibility loci linked with m 6 A modification.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
fishss完成签到 ,获得积分10
1秒前
4秒前
鲁卓林完成签到,获得积分10
5秒前
谨慎纸飞机完成签到,获得积分10
6秒前
轻歌水越完成签到 ,获得积分10
7秒前
夜信完成签到,获得积分10
8秒前
跳跃卿完成签到 ,获得积分10
8秒前
pingli发布了新的文献求助50
8秒前
weiwei完成签到 ,获得积分10
9秒前
顺心醉蝶完成签到 ,获得积分10
11秒前
12秒前
aa完成签到,获得积分10
14秒前
庄怀逸完成签到 ,获得积分10
14秒前
soory完成签到,获得积分10
16秒前
Meng完成签到,获得积分10
16秒前
aumppae完成签到 ,获得积分10
17秒前
one发布了新的文献求助30
18秒前
panda完成签到,获得积分10
18秒前
mendicant完成签到,获得积分10
19秒前
halo完成签到,获得积分10
21秒前
nnnnn完成签到,获得积分10
22秒前
正直的煎饼完成签到,获得积分10
28秒前
djc完成签到,获得积分10
28秒前
ailemonmint完成签到 ,获得积分10
30秒前
jindou完成签到,获得积分10
30秒前
龙虾发票完成签到,获得积分10
31秒前
从容乌完成签到 ,获得积分10
32秒前
32秒前
多多发SCI完成签到,获得积分10
33秒前
康康完成签到 ,获得积分10
34秒前
丘比特应助细心的语蓉采纳,获得10
36秒前
苹果大娘完成签到,获得积分10
37秒前
郭星星完成签到,获得积分10
37秒前
yiming完成签到,获得积分10
38秒前
zxy完成签到,获得积分10
39秒前
科研民工完成签到,获得积分10
39秒前
pingli完成签到,获得积分10
39秒前
天天完成签到 ,获得积分10
39秒前
42秒前
Liang完成签到,获得积分10
44秒前
高分求助中
传播真理奋斗不息——中共中央编译局成立50周年纪念文集(1953—2003) 700
Technologies supporting mass customization of apparel: A pilot project 600
武汉作战 石川达三 500
Chinesen in Europa – Europäer in China: Journalisten, Spione, Studenten 500
Arthur Ewert: A Life for the Comintern 500
China's Relations With Japan 1945-83: The Role of Liao Chengzhi // Kurt Werner Radtke 500
Two Years in Peking 1965-1966: Book 1: Living and Teaching in Mao's China // Reginald Hunt 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3811756
求助须知:如何正确求助?哪些是违规求助? 3356060
关于积分的说明 10379357
捐赠科研通 3073013
什么是DOI,文献DOI怎么找? 1688201
邀请新用户注册赠送积分活动 811860
科研通“疑难数据库(出版商)”最低求助积分说明 766893