PMID- 33247188 OWN - NLM STAT- MEDLINE DCOM- 20210322 LR - 20231213 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Nov 27 TI - Transcriptomic analysis of tobacco-flavored E-cigarette and menthol-flavored E-cigarette exposure in the human middle ear. PG - 20799 LID - 10.1038/s41598-020-77816-2 [doi] LID - 20799 AB - Electronic cigarettes (e-cigarettes) are the most widely used electronic nicotine delivery systems and are designed to imitate smoking and aid in smoking cessation. 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. FAU - Song, Jae-Jun AU - Song JJ AUID- ORCID: 0000-0002-8488-9091 AD - Department of Otolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea. FAU - Go, Yoon Young AU - Go YY AD - Department of Otolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea. FAU - Lee, Jong Kyou AU - Lee JK AD - Department of Otolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1, Daerim 1-dong, Yeongdeunpo-gu, Seoul, 150-950, Korea. FAU - Lee, Bum Sang AU - Lee BS AD - Department of Otolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1, Daerim 1-dong, Yeongdeunpo-gu, Seoul, 150-950, Korea. FAU - Park, Su-Kyoung AU - Park SK AD - Department of Otolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1, Daerim 1-dong, Yeongdeunpo-gu, Seoul, 150-950, Korea. FAU - Jung, Harry AU - Jung H AD - Institute of New Frontier Research Team, Hallym Clinical and Translation Science Institute, Hallym University, Chuncheon, Republic of Korea. FAU - Lee, Jun Ho AU - Lee JH AD - Department of Otolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1, Daerim 1-dong, Yeongdeunpo-gu, Seoul, 150-950, Korea. FAU - Chang, Jiwon AU - Chang J AD - Department of Otolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, 948-1, Daerim 1-dong, Yeongdeunpo-gu, Seoul, 150-950, Korea. brune77@naver.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201127 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Flavoring Agents) RN - 0 (Genetic Markers) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 1490-04-6 (Menthol) SB - IM MH - Cell Line MH - Cell Survival/drug effects MH - Ear, Middle/cytology/*drug effects/metabolism MH - *Electronic Nicotine Delivery Systems MH - Flavoring Agents/*toxicity MH - Gene Expression Profiling MH - Gene Regulatory Networks/drug effects MH - Genetic Markers MH - Humans MH - Menthol/toxicity MH - Proto-Oncogene Mas MH - RNA-Seq MH - Signal Transduction/drug effects/genetics MH - Nicotiana/toxicity PMC - PMC7699635 COIS- The authors declare no competing interests. EDAT- 2020/11/29 06:00 MHDA- 2021/03/23 06:00 PMCR- 2020/11/27 CRDT- 2020/11/28 05:33 PHST- 2019/01/15 00:00 [received] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/11/28 05:33 [entrez] PHST- 2020/11/29 06:00 [pubmed] PHST- 2021/03/23 06:00 [medline] PHST- 2020/11/27 00:00 [pmc-release] AID - 10.1038/s41598-020-77816-2 [pii] AID - 77816 [pii] AID - 10.1038/s41598-020-77816-2 [doi] PST - epublish SO - Sci Rep. 2020 Nov 27;10(1):20799. doi: 10.1038/s41598-020-77816-2.