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Although the number of e-cigarette users is increasing rapidly, especially among young adults and adolescents, the potential health impacts and biologic effects of e-cigarettes still need to be elucidated. Our previous study demonstrated the cytotoxic effects of electronic liquids (e-liquids) in a human middle ear epithelial cell (HMEEC-1) line, which were affected by the manufacturer and flavoring agents regardless of the presence of nicotine. In this study, we aimed to evaluate the gene expression profile and identify potential molecular modulator genes and pathways in HMEEC-1 exposed to two different e-liquids (tobacco- and menthol-flavored). HMEEC-1 was exposed to e-liquids, and RNA sequencing, functional analysis, and pathway analysis were conducted to identify the resultant transcriptomic changes. A total of 843 genes were differentially expressed following exposure to the tobacco-flavored e-liquid, among which 262 genes were upregulated and 581 were downregulated. Upon exposure to the menthol-flavored e-liquid, a total of 589 genes were differentially expressed, among which 228 genes were upregulated and 361 were downregulated. Among the signaling pathways associated with the differentially expressed genes mediated by tobacco-flavored e-liquid exposure, several key molecular genes were identified, including IL6 (interleukin 6), PTGS2 (prostaglandin-endoperoxide synthase 2), CXCL8 (C-X-C motif chemokine ligand 8), JUN (Jun proto-oncogene), FOS (Fos proto-oncogene), and TP53 (tumor protein 53). Under menthol-flavored e-liquid treatment, MMP9 (matrix metallopeptidase 9), PTGS2 (prostaglandin-endoperoxide synthase 2), MYC (MYC proto-oncogene, bHLH transcription factor), HMOX1 (heme oxygenase 1), NOS3 (nitric oxide synthase 3), and CAV1 (caveolin 1) were predicted as key genes. In addition, we identified related cellular processes, including inflammatory responses, oxidative stress and carcinogenesis, under exposure to tobacco- and menthol-flavored e-liquids. We identified differentially expressed genes and related cellular processes and gene signaling pathways after e-cigarette exposure in human middle ear cells. These findings may provide useful evidence for understanding the effect of e-cigarette exposure.<\/jats:p>","DOI":"10.1038\/s41598-020-77816-2","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T11:03:24Z","timestamp":1606475004000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptomic analysis of tobacco-flavored E-cigarette and menthol-flavored E-cigarette exposure in the human middle ear"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8488-9091","authenticated-orcid":false,"given":"Jae-Jun","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Young","family":"Go","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Kyou","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bum Sang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Kyoung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"issue":"Suppl. 2","key":"77816_CR1","doi-asserted-by":"publisher","first-page":"ii4","DOI":"10.1136\/tobaccocontrol-2013-051476","volume":"23","author":"CJ Brown","year":"2014","unstructured":"Brown, C. 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