高级检索
中华医学遗传学杂志
期刊首页
过刊列表
高级检索
稿件发表
• 论著 •
ENGLISH ABSTRACT
人胃食管交界处腺癌mRNA m7G修饰情况的初步分析
刘滋验
王晓燕
胡滨滨
张诗琪
郎亚昆
范钰
作者及单位信息
·
DOI： 10.3760/cma.j.cn511374-20240724-00408
Preliminary analysis of mRNA m7G modifications in human Adenocarcinoma of esophagogastric junction
Liu Ziyan
Wang Xiaoyan
Hu Binbin
Zhang Shiqi
Lang Yakun
Fan Yu
Authors Info & Affiliations
Liu Ziyan
Institute of Tumor Research, People′s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu 212002, China
Wang Xiaoyan
Department of Gastroenterology, Suqian First People′s Hospital, Nanjing Medical University, Suqian, Jiangsu 223812, China
Hu Binbin
Institute of Tumor Research, People′s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu 212002, China
Zhang Shiqi
Department of Gastroenterology, Suqian First People′s Hospital, Nanjing Medical University, Suqian, Jiangsu 223812, China
Lang Yakun
Institute of Tumor Research, People′s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu 212002, China
Fan Yu
Institute of Tumor Research, People′s Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu 212002, China
·
DOI： 10.3760/cma.j.cn511374-20240724-00408
25
6
0
0
0
0
PDF下载
APP内阅读
摘要

目的探讨mRNA m7G修饰在人胃食管交界处腺癌(AEG)发生发展中的潜在作用。

方法选取2018年至2019年就诊于江苏大学附属人民医院的4例接受手术治疗的AEG患者病理组织标本为研究对象。收集患者AEG组织与癌旁正常组织，提取RNA样品后进行m7G甲基化RNA免疫共沉淀测序(m7G-MeRIP-seq)，分析2组m7G修饰模式、m7G修饰差异位点特征、差异表达mRNA特征、差异m7G修饰与mRNA表达量的相关性。应用甲基化RNA免疫共沉淀实时荧光定量PCR(MeRIP-qPCR)对差异m7G修饰位点基因( MSH6、BRCA1、SOX9)进行验证。应用实时荧光定量PCR(RT-qPCR)分析 METTL1与 WDR4基因在2组间的表达情况。本研究已通过江苏省大学附属人民医院医学伦理委员会的审查(批准号：伦研批第20150083号)。

结果①m7G-MeRIP-seq分析结果显示，AEG组织与癌旁正常组织的m7G修饰主要位于mRNA内部起始密码子GC富集区，2组间m7G修饰差异位点基因与癌症密切相关。②mRNA文库分析结果显示，2组间差异表达mRNA在AEG组织中主要呈上调趋势，在癌旁正常组织中主要呈下调趋势。③交叉分析结果显示，AEG组织中超甲基化修饰基因倾向于表达上调，低甲基化修饰基因倾向于表达下调。④MeRIP-qPCR验证结果显示，AEG组织中 MSH6、BRCA1和 SOX9基因mRNA表达量均上调(AEG组织比癌旁正常组织， P<0.05)。⑤RT-qPCR检测结果显示，AEG组织中 METTL1与 WDR4基因mRNA表达量均上调(AEG组织比癌旁正常组织， P<0.000 5)。

结论上述研究成果揭示mRNA m7G修饰可能在AEG的发生与发展中发挥重要作用，METTL1和WDR4蛋白可能通过调节mRNA m7G修饰进而促进AEG的进程，为AEG的分子机制研究与治疗提供相关依据。

m7G修饰;胃食管交界处腺癌;mRNA甲基化;甲基化RNA免疫共沉淀;METTL1/WDR4蛋白复合体
ABSTRACT

ObjectiveTo explore the potential role of mRNA m7G modification in the pathogenesis of human adenocarcinoma of esophagogastric junction (AEG).

MethodsPathological tissue specimens from four AEG patients who underwent surgical treatment at the People′s Hospital Affiliated to Jiangsu University between 2018 and 2019 were selected. Tumor tissues and adjacent normal tissues were collected from these patients. RNA was extracted from both tissue types and subjected to m7G methylated RNA immunoprecipitation sequencing (m7G-MeRIP-seq) to analyze the patterns of m7G modification, the characteristics of differential m7G modification sites, the differentially expressed mRNA, and the correlation between m7G modification and mRNA expression levels. Differential m7G-modified genes ( MSH6, BRCA1, and SOX9) were further validated using methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR), while the expression of METTL1 and WDR4 genes was examined by real-time quantitative PCR (RT-qPCR). This study was approved by the Medical Ethics Committee of the People′s Hospital Affiliated to Jiangsu University (Ethics No. 20150083).

Results① m7G-MeRIP-seq analysis revealed that m7G modifications in both AEG and adjacent normal tissues were predominantly located in the GC-rich region surrounding the internal start codon of mRNA. Differential m7G modification sites between the two groups were closely associated with cancer-related genes. ② mRNA library analysis showed that differentially expressed mRNA were predominantly upregulated in AEG tissues and downregulated in adjacent normal tissues. ③ Cross-analysis indicated that genes with hypermethylation tended to exhibit upregulated expression, while genes with hypomethylation were typically downregulated in AEG tissues. ④ MeRIP-qPCR validation confirmed that the mRNA expression of MSH6, BRCA1, and SOX9 were significantly upregulated in AEG tissues compared to adjacent normal tissues (AEG vs. normal, P<0.05). ⑤ RT-qPCR results demonstrated that the mRNA expression levels of METTL1 and WDR4 were also upregulated in AEG tissues (AEG vs. normal, P<0.000 5).

ConclusionThese findings suggest that mRNA m7G modification plays a significant role in the development of AEG. Furthermore, proteins as METTL1 and WDR4 may facilitate AEG progression by regulating mRNA m7G modification. These results provide valuable insights into the molecular mechanisms underlying AEG and may inform future therapeutic strategies for this malignancy.

m7G modification;Adenocarcinoma of esophagogastric junction;RNA methylation;Methylated RNA immunoprecipitation;METTL1/WDR4 protein complex
Fan Yu, Email: nc.defudabe.sju54321fuy
Lang Yakun, Email: mocdef.qabq868969348
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

刘滋验,王晓燕,胡滨滨,等. 人胃食管交界处腺癌mRNA m7G修饰情况的初步分析[J]. 中华医学遗传学杂志,2025,42(02)：187-197.

DOI:10.3760/cma.j.cn511374-20240724-00408

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

自20世纪90年代起，针对表观领域的研究逐渐兴起，其研究范围广泛，主要涉及DNA甲基化、RNA甲基化、组蛋白修饰、非编码RNA修饰和染色质重排等生物学过程。随着研究的不断深入，"表观遗传学"一词用于描述RNA携带的化学修饰对基因表达和RNA-蛋白相互作用的影响 [ 1 ]。截至目前，人体内已鉴定出100多种RNA化学修饰，可影响RNA的剪接、定位及稳定性 [ 2 , 3 ]。一些RNA修饰具有可逆性与动态性，细胞可以通过这些修饰调节相关基因表达与生理过程，包括脂肪形成、精子发生、发育、癌变与干细胞更新等 [ 4 , 5 , 6 ]。
常见的RNA甲基化修饰包括5-甲基胞嘧啶(m5C) [ 7 ]、N1-甲基腺苷(m1A) [ 8 , 9 ]、N6-甲基腺苷(m6A) [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]、N7-甲基鸟苷(m7G) [ 10 ]，其中m7G修饰是真核信使RNA(mRNA)、长链非编码RNA(long non-coding RNA，lncRNA)和微RNA(miRNA)中最普遍的修饰 [ 17 ]。不同类型RNA内部m7G修饰具有不同的功能，包括调节mRNA转录、miRNA生物合成、转运RNA(tRNA)稳定性以及18S核糖体RNA(18S rRNA)核加工和成熟等 [ 18 ]。原核生物、真核生物和古细菌中均存在m7G修饰 [ 19 ]。在真核生物中，m7G修饰主要位于mRNA的5′端帽结构(5′ Cap)中，可调控mRNA生命周期的每个阶段包括转录、剪接与核输出 [ 20 , 21 , 22 ]。tRNA中m7G修饰位点通常位于可变环区G46核苷酸位点，由METTL1/WDR4复合物介导，可提高tRNA三维核心结构的稳定性 [ 23 , 24 , 25 ]。18S rRNA中m7G修饰位点通常位于第1 639核苷酸位点，同样由METTL1/WDR4复合物介导 [ 26 , 27 , 28 , 29 ]。有研究使用差异酶切(S1核酸酶或磷酸二酯酶Ⅰ)结合液相色谱-串联质谱连用技术分析发现，在高等真核生物mRNA内部结构也存在m7G修饰，进一步揭示m7G修饰在真核生物转录后基因调控过程中发挥重要功能 [ 30 ]。Zhang等 [ 31 ]利用甲基化RNA免疫共沉淀测序(methylated RNA immunoprecipitation sequencing，MeRIP-seq)技术揭示了人体细胞mRNA内部m7G修饰主要富集于3′端非翻译编码区(3′ UTR)和5′端非翻译编码区(5′ UTR)，在编码区(CDS)分布保守。
上消化道肿瘤是世界范围内癌症相关死亡的主要原因 [ 32 ]。由于胃食管交界处的特殊解剖位置，胃食管交界处腺癌(adenocarcinoma of esophagogastric junction，AEG)已不同程度地纳入食管癌和胃癌的研究。近几十年来，无论是西方还是东方国家，AEG的发病率均有明显上升 [ 33 ]。多数AEG患者诊断较晚，生存率较差，5年生存率不足20% [ 34 ]。由于AEG的危险因素尚不清楚，临床缺乏早期诊断和预后预测的生物标志物，亟待深入的分子机制研究 [ 35 ]。为探究mRNA m7G修饰在AEG发生发展中的作用，本研究以AEG组织及其癌旁正常组织样本为研究对象，应用MeRIP-seq技术 [ 36 ]对组织样本转录组mRNA m7G修饰情况进行分析，可为进一步探讨mRNA m7G修饰在AEG发病机制中的潜在作用提供依据。现将研究结果报道如下。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Ji LJ , Chen XM . Regulation of small RNA stability: methylation and beyond[J]. Cell Res, 2012,22(4):624-636. DOI: 10.1038/cr.2012.36 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Boccaletto P , Machnicka MA , Purta E ,et al. Modomics: a database of RNA modification pathways. 2017 update[J]. Nucleic Acids Res, 2018,46(D1):D303-D307. DOI: 10.1093/nar/gkx1030 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Roundtree IA , Evans ME , Pan T ,et al. Dynamic RNA modifications in gene expression regulation[J]. Cell, 2017,169(7):1187-1200. DOI: 10.1016/j.cell.2017.05.045 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Gilbert WV , Bell TA , Schaening C . Messenger RNA modifications: form, distribution, and function[J]. Science, 2016,352(6292):1408-1412. DOI: 10.1126/science.aad8711 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Li S , Mason CE . The pivotal regulatory landscape of RNA modifications[J]. Annu Rev Genomics Hum Genet, 2014,15:127-150. DOI: 10.1146/annurev-genom-090413-025405 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Song JH , Yi CQ . Chemical modifications to RNA: a new layer of gene expression re gulation [J]. ACS Chem Biol, 2017,12(2):316-325. DOI: 10.1021/acschembio.6b00960 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Edelheit S , Schwartz S , Mumbach MR ,et al. Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m5C within archaeal mRNAs[J]. PLoS Genet, 2013,9(6):e1003602. DOI: 10.1371/journal.pgen.1003602 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Dominissini D , Nachtergaele S , Moshitch-Moshkovitz S ,et al. The dynamic n(1)-methyladenosine methylome in eukaryotic messenger RNA[J]. Nature, 2016,530(7591):441-446. DOI: 10.1038/nature16998 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Li XY , Xiong XS , Wang K ,et al. Transcriptome-wide mapping reveals reversible and dynamic n(1)-methyladenosine methylome[J]. Nat Chem Biol, 2016,12(5):311-316. DOI: 10.1038/nchembio.2040 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Dominissini D , Moshitch-Moshkovitz S , Schwartz S ,et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq[J]. Nature, 2012,485(7397):201-206. DOI: 10.1038/nature11112 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Wang Y , Li Y , Toth JI ,et al. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells[J]. Nat Cell Biol, 2014,16(2):191-198. DOI: 10.1038/ncb2902 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Wang X , Zhao BS , Roundtree IA ,et al. N(6)-methyladenosine modulates messenger RNA translation efficiency[J]. Cell, 2015,161(6):1388-1399. DOI: 10.1016/j.cell.2015.05.014 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Zhou J , Wan J , Gao XW ,et al. Dynamic m(6)A mRNA methylation directs translational control of heat shock response[J]. Nature, 2015,526(7574):591-594. DOI: 10.1038/nature15377 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Roost C , Lynch SR , Batista PJ ,et al. Structure and thermodynamics of n6-methyladenosine in RNA: a spring-loaded base modification[J]. J Am Chem Soc, 2015,137(5):2107-2115. DOI: 10.1021/ja513080v .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Xiao W , Adhikari S , Dahal U ,et al. Nuclear m(6)A reader ythdc1 regulates mRNA splicing[J]. Mol Cell, 2016,61(4):507-519. DOI: 10.1016/j.molcel.2016.01.012 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Fustin JM , Doi M , Yamaguchi Y ,et al. RNA-methylation-dependent RNA processing controls the speed of the circadian clock[J]. Cell, 2013,155(4):793-806. DOI: 10.1016/j.cell.2013.10.026 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Ke S , Alemu EA , Mertens C ,et al. A majority of m6A residues are in the last exons, allowing the potential for 3′ utr regulation[J]. Genes Dev, 2015,29(19):2037-2053. DOI: 10.1101/gad.269415.115 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Yang ZY , Zhang SY , Xia T ,et al. RNA modifications meet tumors[J]. Cancer Manag Res, 2022,14:3223-3243. DOI: 10.2147/cmar.S391067 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Enroth C , Poulsen LD , Iversen S ,et al. Detection of internal n7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing[J]. Nucleic Acids Res, 2019,47(20):e126. DOI: 10.1093/nar/gkz736 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Konarska MM , Padgett RA , Sharp PA . Recognition of cap structure in splicing in vitro of mRNA precursors [J]. Cell, 1984,38(3):731-736. DOI: 10.1016/0092-8674(84)90268-x .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Lewis JD , Izaurralde E . The role of the cap structure in RNA processing and nuclear export[J]. Eur J Biochem, 1997,247(2):461-469. DOI: 10.1111/j.1432-1033.1997.00461.x .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Pei Y , Shuman S . Interactions between fission yeast mRNA capping enzymes and elongation factor spt5[J]. J Biol Chem, 2002,277(22):19639-19648. DOI: 10.1074/jbc.M200015200 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Alexandrov A , Martzen MR , Phizicky EM . Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA[J]. RNA, 2002,8(10):1253-1266. DOI: 10.1017/s1355838202024019 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Du D , He J , Ju CX ,et al. When n(7)-methyladenosine modification meets cancer: Emerging frontiers and promising therapeutic opportunities[J]. Cancer Lett, 2023,562:216165. DOI: 10.1016/j.canlet.2023.216165 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Guy MP , Phizicky EM . Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification[J]. RNA Biol, 2014,11(12):1608-1618. DOI: 10.1080/15476286.2015.1008360 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Figaro S , Wacheul L , Schillewaert S ,et al. Trm112 is required for bud23-mediated methylation of the 18s rRNA at position g1575[J]. Mol Cell Biol, 2012,32(12):2254-2267. DOI: 10.1128/mcb.06623-11 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Haag S , Kretschmer J , Bohnsack MT . Wbscr22/merm1 is required for late nuclear pre-ribosomal RNA processing and mediates n7-methylation of g1639 in human 18s rRNA[J]. RNA, 2015,21(2):180-187. DOI: 10.1261/rna.047910.114 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Sloan KE , Warda AS , Sharma S ,et al. Tuning the ribosome: the influence of rRNA modification on eukaryotic ribosome biogenesis and function[J]. RNA Biol, 2017,14(9):1138-1152. DOI: 10.1080/15476286.2016.1259781 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Zorbas C , Nicolas E , Wacheul L ,et al. The human 18s rRNA base methyltransferases dimt1l and wbscr22-trmt112 but not rRNA modification are required for ribosome biogenesis [J]. Mol Biol Cell, 2015,26(11):2080-2095. DOI: 10.1091/mbc.E15-02-0073 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Chu JM , Ye TT , Ma CJ ,et al. Existence of internal n7-methylguanosine modification in mRNA determined by differential enzyme treatment coupled with mass spectrometry analysis[J]. ACS Chem Biol, 2018,13(12):3243-3250. DOI: 10.1021/acschembio.7b00906 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Zhang LS , Liu C , Ma HH ,et al. Transcriptome-wide mapping of internal n(7)-methylguanosine methylome in mammalian mRNA[J]. Mol Cell, 2019,74(6):1304-1316.e8. DOI: 10.1016/j.molcel.2019.03.036 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Ashraf N , Hoffe S , Kim R . Locally advanced gastroesophageal junction tumor: a treatment dilemma[J]. Oncologist, 2015,20(2):134-142. DOI: 10.1634/theoncologist.2014-0377 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Pastina M , Menna C , Andreetti C ,et al. The esophagogastric junctional adenocarcinoma an increasing disease[J]. J Thorac Dis, 2017,9(6):1455-1458. DOI: 10.21037/jtd.2017.05.70 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Agarwal S , Bell MG , Dhaliwal L ,et al. Population based time trends in the epidemiology and mortality of gastroesophageal junction and esophageal adenocarcinoma[J]. Dig Dis Sci, 2024,69(1):246-253. DOI: 10.1007/s10620-023-08126-6 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Bartley AN , Washington MK , Colasacco C ,et al. Her2 testing and clinical decision making in gastroesophageal adenocarcinoma：guideline from the college of American pathologists, American society for clinical pathology, and the American society of clinical oncology[J]. J Clin Oncol, 2017,35(4):446-464. DOI: 10.1200/jco.2016.69.4836 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Zhao BS , Roundtree IA , He C . Post-transcriptional gene regulation by mRNA modifications[J]. Nat Rev Mol Cell Biol, 2017,18(1):31-42. DOI: 10.1038/nrm.2016.132 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Martin MJEJ . Cutadapt removes adapter sequences from high-throughput sequencing reads[J]. 2011,17:10-12.
返回引文位置Google Scholar
百度学术
万方数据
[38]
Kim D , Langmead B , Salzberg SL . Hisat: a fast spliced aligner with low memory requirements[J]. Nat Methods, 2015,12(4):357-360. DOI: 10.1038/nmeth.3317 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Zhang Y , Liu T , Meyer CA ,et al. Model-based analysis of chip-seq (macs)[J]. Genome Biol, 2008,9(9):R137. DOI: 10.1186/gb-2008-9-9-r137 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Shen L , Shao NY , Liu XC ,et al. Diffreps: detecting differential chromatin modification sites from chip-seq data with biological replicates[J]. PLoS One, 2013,8(6):e65598. DOI: 10.1371/journal.pone.0065598 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Gao ZJ , Xu JY , Zhang ZP ,et al. A comprehensive analysis of METTL1 to immunity and stemness in pan-cancer[J]. Front Immunol, 2022,13:795240. DOI: 10.3389/fimmu.2022.795240 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Yang X , Yang Y , Sun BF ,et al. 5-methylcytosine promotes mRNA export - nsun2 as the methyltransferase and alyref as an m(5)C reader[J]. Cell Res, 2017,27(5):606-625. DOI: 10.1038/cr.2017.55 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Ge S , Li BF , Li YY ,et al. Genomic alterations in a dvanced gastric cancer endoscopic biopsy samples using targeted next-generation sequencing [J]. Am J Cancer Res, 2017,7(7):1540-1553.
返回引文位置Google Scholar
百度学术
万方数据
[44]
Liu Y , Chen H , Xiao LS ,et al. Notum enhances gastric cancer stem-like cell properties through upregulation of sox2 by pi3k/akt signaling pathway[J]. Cell Oncol (Dordr), 2024,47(2):463-480. DOI: 10.1007/s13402-023-00875-w .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Lu Y , Huang PP , Zeng XL ,et al. Inhibition of fndc1 suppresses gastric cancer progression by interfering with gβγ-vegfr2 complex formation[J]. iScience, 2023,26(9):107534. DOI: 10.1016/j.isci.2023.107534 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Shi KH , Xue H , Zhao EH ,et al. Krt80 expression works as a biomarker and a target for differentiation in gastric cancer[J]. Histol Histopathol, 2024,39(1):117-130. DOI: 10.14670/hh-18-618 .
返回引文位置Google Scholar
百度学术
万方数据
[47]
Aldaz P , Otaegi-Ugartemendia M , Saenz-Antoñanzas A ,et al. Sox9 promotes tumor progression through the axis bmi1-p21(cip)[J]. Sci Rep, 2020,10(1):357. DOI: 10.1038/s41598-019-57047-w .
返回引文位置Google Scholar
百度学术
万方数据
[48]
Corvalán RA . Bases epigenéticas del cáncer gástrico: oportunidades para la búsqueda de nuevos biomarcadores [epigenetics in the pathogenesis and early detection of gastric cancer ] [J]. Rev Med Chil, 2013,141(12):1570-1577. DOI: 10.4067/s0034-98872013001200011 .
返回引文位置Google Scholar
百度学术
万方数据
[49]
Dracea A , Angelescu C , Danciulescu M ,et al. Mismatch repair gene expression in gastroesophageal cancers[J]. Turk J Gastroenterol, 2015,26(5):373-377. DOI: 10.5152/tjg.2015.0139 .
返回引文位置Google Scholar
百度学术
万方数据
[50]
Shimotohno K , Kodama Y , Hashimoto J ,et al. Importance of 5′-terminal blocking structure to stabilize mRNA in eukaryotic protein synthesis [J]. Proc Natl Acad Sci U S A, 1977,74(7):2734-2738. DOI: 10.1073/pnas.74.7.2734 .
返回引文位置Google Scholar
百度学术
万方数据
[51]
Culjkovic B , Topisirovic I , Skrabanek L ,et al. Eif4e is a central node of an RNA regulon that governs cellular proliferation[J]. J Cell Biol, 2006,175(3):415-426. DOI: 10.1083/jcb.200607020 .
返回引文位置Google Scholar
百度学术
万方数据
[52]
Katsara O , Schneider RJ . M(7)G tRNA modification reveals new secrets in the translational regulation of cancer development[J]. Mol Cell, 2021,81(16):3243-3245. DOI: 10.1016/j.molcel.2021.07.030 .
返回引文位置Google Scholar
百度学术
万方数据
[53]
Topisirovic I , Svitkin YV , Sonenberg N ,et al. Cap and cap-binding proteins in the control of gene expression[J]. Wiley Interdiscip Rev RNA, 2011,2(2):277-298. DOI: 10.1002/wrna.52 .
返回引文位置Google Scholar
百度学术
万方数据
[54]
Dewe JM , Whipple JM , Chernyakov I ,et al. The yeast rapid tRNA decay pathway competes with elongation factor 1a for substrate tRNAs and acts on tRNAs lacking one or more of several modifications[J]. RNA, 2012,18(10):1886-1896. DOI: 10.1261/rna.033654.112 .
返回引文位置Google Scholar
百度学术
万方数据
[55]
Malbec L , Zhang T , Chen YS ,et al. Dynamic methylome of internal mRNA n(7)-methylguanosine and its regulatory role in translation[J]. Cell Res, 2019,29(11):927-941. DOI: 10.1038/s41422-019-0230-z .
返回引文位置Google Scholar
百度学术
万方数据
[56]
Xia XH , Wang Y , Zheng JC . Internal m7G methylation: a novel epitranscriptomic contributor in brain development and diseases[J]. Mol Ther Nucleic Acids, 2023,31:295-308. DOI: 10.1016/j.omtn.2023.01.003 .
返回引文位置Google Scholar
百度学术
万方数据
[57]
Boulias K , Greer EL . Put the pedal to the METTL1: adding internal m(7)G increases mRNA translation efficiency and augments miRNA processing[J]. Mol Cell, 2019,74(6):1105-1107. DOI: 10.1016/j.molcel.2019.06.004 .
返回引文位置Google Scholar
百度学术
万方数据
[58]
Ruiz-Arroyo VM , Raj R , Babu K ,et al. Structures and mechanisms of tRNA methylation by METTL1-WDR4[J]. Nature, 2023,613(7943):383-390. DOI: 10.1038/s41586-022-05565-5 .
返回引文位置Google Scholar
百度学术
万方数据
[59]
Li JZ , Wang LF , Hahn Q ,et al. Structural basis of regulated m(7)G tRNA modification by METTL1-WDR4[J]. Nature, 2023,613(7943):391-397. DOI: 10.1038/s41586-022-05566-4 .
返回引文位置Google Scholar
百度学术
万方数据
[60]
Cheng WL , Gao AL , Lin H ,et al. Novel roles of METTL1/WDR4 in tumor via m(7)G methylation[J]. Mol Ther Oncolytics, 2022,26:27-34. DOI: 10.1016/j.omto.2022.05.009 .
返回引文位置Google Scholar
百度学术
万方数据
[61]
Tian QH , Zhang MF , Zeng JS ,et al. METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via pten[J]. J Mol Med (Berl), 2019,97(11):1535-1545. DOI: 10.1007/s00109-019-01830-9 .
返回引文位置Google Scholar
百度学术
万方数据
[62]
Chen ZH , Zhu WJ , Zhu SH ,et al. METTL1 promotes hepatocarcinogenesis via m(7)G tRNA modification-dependent translation control[J]. Clin Transl Med, 2021,11(12):e661. DOI: 10.1002/ctm2.661 .
返回引文位置Google Scholar
百度学术
万方数据
[63]
Chen J , Li K , Chen JW ,et al. Aberrant translation regulated by METTL1/WDR4-mediated tRNA n7-methylguanosine modification drives head and neck squamous cell carcinoma progression[J]. Cancer Commun (Lond), 2022,42(3):223-244. DOI: 10.1002/cac2.12273 .
返回引文位置Google Scholar
百度学术
万方数据
[64]
Ying XL , Liu BX , Yuan ZS ,et al. METTL1-m(7)G-egfr/efemp1 axis promotes the bladder cancer development[J]. Clin Transl Med, 2021,11(12):e675. DOI: 10.1002/ctm2.675 .
返回引文位置Google Scholar
百度学术
万方数据
[65]
Han H , Yang CL , Ma JY ,et al. N(7)-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the rptor/ulk1/autophagy axis[J]. Nat Commun, 2022,13(1):1478. DOI: 10.1038/s41467-022-29125-7 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
范钰，Email： nc.defudabe.sju54321fuy
B
郎亚昆，Email： mocdef.qabq868969348
C

刘滋验：实施研究、采集数据、分析数据、起草文章、统计分析；王晓燕：酝酿和设计实验、获取研究经费、行政、技术支持；胡滨滨：采集数据、分析数据；张诗琪：采集数据、统计分析、获取研究经费；郎亚昆：分析数据、指导论文；范钰：酝酿和设计实验、分析数据、统计分析、获取研究经费、指导论文

D
所有作者均声明不存在利益冲突
E
江苏省卫生健康委员会重点项目基金 (ZD2022052、K2023016)
宿迁第一人民医院科研项目基金 (KY202203)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
最新推荐
更多
腹腔镜或机器人辅助胰腺癌根治术中国专家共识（2022年版）
中国抗癌协会胰腺癌专业委员会微创诊治学组 等
中华外科杂志 2023,61(03)
乳腺癌患者血浆中miR-501-5p、CLCA4 mRNA的表达及其诊断价值
陈慧莉 等
中国医师杂志 2022,24(06)
社区老年人衰弱情况及其影响因素研究
冯青青 等
中国全科医学 2021,24(24)
mRNA甲基化修饰N6-甲基腺苷对糖尿病胰岛β细胞功能的调控作用
谢建军 等
中华糖尿病杂志 2020,12(12)
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大