{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:47:44Z","timestamp":1788918464889,"version":"build-2803163510"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:00:00Z","timestamp":1607472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8177051154"],"award-info":[{"award-number":["8177051154"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>There are associations between DNA methylation and the expression of long non-coding RNA (lncRNA), also known as lncRNA expression quantitative trait methylations (lnc-eQTMs). Lnc-eQTMs may induce a wide range of carcinogenesis pathways. However, lnc-eQTMs have not been globally identified and studied, and their roles in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) are largely unknown. In the present study, we identified some differential methylation sites located in genes of long intergenic non-coding RNAs (lincRNAs) and other types of lncRNAs in LUAD and LUSC. An integrated pipeline was established to construct two global cancer-specific regulatory networks of lnc-eQTMs in LUAD and LUSC. The associations between eQTMs showed common and specific features between LUAD and LUSC. Some lnc-eQTMs were also related with survival in LUAD- and LUSC-specific regulatory networks. Lnc-eQTMs were associated with cancer-related functions, such as lung epithelium development and vasculogenesis by functional analysis. Drug repurposing analysis revealed that these lnc-eQTMs may mediate the effects of some anesthesia-related drugs in LUAD and LUSC. In summary, the present study elucidates the roles of lnc-eQTMs in LUAD and LUSC, which could improve our understanding of lung cancer pathogenesis and facilitate treatment.<\/jats:p>","DOI":"10.3389\/fgene.2020.602035","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T08:41:32Z","timestamp":1607503292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of Potential Long Non-coding RNA Expression Quantitative Trait Methylations in Lung Adenocarcinoma and Lung Squamous Carcinoma"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaohong","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlong","family":"Bu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoding","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangwei","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guonian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.21873\/anticanres.13100","article-title":"Etomidate Suppresses Invasion and Migration of Human A549 Lung Adenocarcinoma Cells.","volume":"39","author":"Chu","year":"2019","journal-title":"Antican. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.pharmthera.2019.02.010","article-title":"Nanotechnology in the diagnosis and treatment of lung cancer.","volume":"198","author":"Cryer","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1007\/s12253-019-00780-4","article-title":"Comprehensive Analysis of Aberrantly Expressed Profiles of lncRNAs and miRNAs with Associated ceRNA Network in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.","volume":"26","author":"Dong","year":"2020","journal-title":"Pathol. Oncol. Res. POR"},{"key":"B4","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/labinvest.2015.123","article-title":"Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells.","volume":"96","author":"Fang","year":"2016","journal-title":"Lab. Invest."},{"key":"B5","doi-asserted-by":"crossref","first-page":"D1028","DOI":"10.1093\/nar\/gky1096","article-title":"Lnc2Cancer v2.0: updated database of experimentally supported long non-coding RNAs in human cancers.","volume":"8","author":"Gao","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20081924","article-title":"Long noncoding RNA and epithelial mesenchymal transition in cancer.","volume":"20","author":"Gugnoni","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"247","DOI":"10.2217\/epi.14.80","article-title":"Genetic alterations of DNA methylation machinery in human diseases.","volume":"7","author":"Hamidi","year":"2015","journal-title":"Epigenomics"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0360","article-title":"NSD3-induced methylation of H3K36 activates NOTCH signaling to drive breast tumor initiation and metastatic progression.","author":"Jeong","year":"2020","journal-title":"Cancer Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.imbio.2013.11.004","article-title":"Lung cancer neovascularisation: Cellular and molecular interaction between endothelial and lung cancer cells.","volume":"219","author":"Kaessmeyer","year":"2014","journal-title":"Immunobiology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update.","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.ajpath.2012.08.042","article-title":"Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma.","volume":"182","author":"Li","year":"2013","journal-title":"Am. J. Pathol."},{"key":"B12","first-page":"5748","article-title":"Effects of etomidate and propofol on immune function in patients with lung adenocarcinoma.","volume":"8","author":"Liu","year":"2016","journal-title":"Am. J. Translat. Res."},{"key":"B13","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/gcc.22709","article-title":"Long noncoding RNA expression profiling in cancer: Challenges and opportunities.","volume":"58","author":"Lorenzi","year":"2019","journal-title":"Genes Chromosomes Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s12272-019-01126-z","article-title":"Targeting epigenetics for cancer therapy.","volume":"42","author":"Park","year":"2019","journal-title":"Archiv. Pharm. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/nrc.2017.84","article-title":"Understanding and targeting resistance mechanisms in NSCLC.","volume":"25","author":"Rotow","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1002\/ijc.29929","article-title":"Fifty years of the International Agency for Research on Cancer (1965 to 2015).","volume":"15","author":"Saracci","year":"2016","journal-title":"Int. J. Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature14192","article-title":"Function and information content of DNA methylation.","volume":"15","author":"Schubeler","year":"2015","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020.","volume":"70","author":"Siegel","year":"2020","journal-title":"CA A Cancer J. Clinic."},{"key":"B19","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/s0006-2952(00)00377-4","article-title":"Inhibition of glucose transport and direct interactions with type 1 facilitative glucose transporter (GLUT-1) by etomidate, ketamine, and propofol: a comparison with barbiturates.","volume":"1","author":"Stephenson","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"B20","doi-asserted-by":"crossref","first-page":"L1049","DOI":"10.1152\/ajplung.00244.2018","article-title":"Activation of the mTORC1\/PGC-1 axis promotes mitochondrial biogenesis and induces cellular senescence in the lung epithelium.","volume":"1","author":"Summer","year":"2019","journal-title":"Am. J. Physiol. Lung Cell. Mole.physiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.pharmthera.2019.06.005","article-title":"Drug resistance in non-small cell lung Cancer (NSCLC): Impact of genetic and non-genetic alterations on therapeutic regimen and responsiveness.","volume":"202","author":"Terlizzi","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1089\/cmb.2019.0164","article-title":"Distinct Patterns of mRNA and lncRNA Expression Differences Between Lung Squamous Cell Carcinoma and Adenocarcinoma.","volume":"27","author":"Tian","year":"2020","journal-title":"J. Comput. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1126\/science.1192002","article-title":"Long noncoding RNA as modular scaffold of histone modification complexes.","volume":"6","author":"Tsai","year":"2010","journal-title":"Science."},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.1007\/s13277-016-5422-2","article-title":"Transcriptome analysis of distinct long non-coding RNA transcriptional fingerprints in lung adenocarcinoma and squamous cell carcinoma.","volume":"37","author":"Wei","year":"2016","journal-title":"Tumour Biol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109192","article-title":"Involvement of noncoding RNAs in epigenetic modifications of esophageal cancer.","volume":"117","author":"Xiao","year":"2019","journal-title":"Biomed. Pharm."},{"key":"B26","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.canlet.2015.08.008","article-title":"Long noncoding RNA, the methylation of genomic elements and their emerging crosstalk in hepatocellular carcinoma.","volume":"1","author":"Yuan","year":"2016","journal-title":"Cancer lett."},{"key":"B27","doi-asserted-by":"crossref","first-page":"D133","DOI":"10.1093\/nar\/gkx985","article-title":"Lnc2Meth: a manually curated database of regulatory relationships between long non-coding RNAs and DNA methylation associated with human disease.","volume":"4","author":"Zhi","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2020.602035\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T08:41:36Z","timestamp":1607503296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2020.602035\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,9]]},"references-count":27,"alternative-id":["10.3389\/fgene.2020.602035"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2020.602035","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,9]]},"article-number":"602035"}}