Transcriptomic analysis of tobacco-flavored E-cigarette and menthol-flavored E-cigarette exposure in the human middle ear

Abstract

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.

Impact of Electronic Cigarettes on the Upper Aerodigestive Tract: A Comprehensive Review for Otolaryngology Providers

“… 172 , 173 In the larynx, rats exposed to e‐cig aerosols showed early evidence of hyperplasia and metaplasia of the mucosa, 174 although the results were not statistically significant in this limited study, and increases in IL‐4. 175 In addition, both nicotine‐containing and nicotine‐free e‐juice have been found to cause biologic disruptions including oxidative stress, DNA breakage, metanuclear anomalies, liposomal dysfunction, and solvent and lipid accumulation, and cytotoxicity in human gingival fibroblasts, 67 , 176 , 177 , 178 , 179 , 180 vocal fold epithelial cells and fibroblasts, 181 , 182 head and neck squamous cell carcinoma cell lines, 67 , 183 , 184 , 185 noncancerous oral and oropharyngeal epithelial cells, 139 , 178 , 186 , 187 , 188 , 189 , 190 , 191 , 192 middle ear epithelial cells, 193 , 194 , 195 nasal epithelial cells, 196 , 197 and organotypic cultures/organoids. 178 , 182 , 197 Interestingly, a recent study found that oral cancer cells exposed to e‐cig aerosols increased cell resistance to cisplatin through changes in drug transporters, suggesting a mechanism for e‐cig‐induced chemotherapy resistance.…”

Assessment of factors associated with PSA level in prostate cancer cases and controls from three geographical regions

“…In vitro studies with tobacco (TFeL) and menthol (MFeL) flavoured e-liquids have shown 843 and 589 differentially regulated genes. MFeL have affected several pathways including metabolic pathways as well as steroid hormone biosynthesis, including the AKR1C1, AKR1C2 and AKR1C3 genes 58 . The authors have also shown that the MFeL increased AKR1C1 gene expression by 7.4-fold compared to AKR1C1 gene expression increase of 4.9-fold by TFeL.…”

Still water run deep: Therapeutic TP effect of ucMSC‐Ex via regulating mTOR to enhance autophagy

“…An increasing number of studies are uncovering the genetic basis of multiple phenotypic traits through comprehensive analysis of whole transcriptome resequencing data 17 . Analysis of transcriptome data can help to reveal the effects of experimental variables on cellular life activities at the gene expression level 18 . In this study, we performed whole transcriptome resequencing of pancreatic tissue from TP rats after ucMSC‐Ex treatment to identify significantly altered cellular activities and target gene expression.…”

“… 17 Analysis of transcriptome data can help to reveal the effects of experimental variables on cellular life activities at the gene expression level. 18 In this study, we performed whole transcriptome resequencing of pancreatic tissue from TP rats after ucMSC‐Ex treatment to identify significantly altered cellular activities and target gene expression. Subsequently, we confirmed that ucMSC‐Ex exerted therapeutic effects after TP by enhancing autophagy through the regulation of mTOR.…”