Electronic cigarettes (ECIGs) are electronic devices that heat and vaporize a solution that usually contains a mixture of glycerol, propylene glycol, water, flavors and various concentrations of nicotine. ECIGs have 3 key components: A power source, a cartridge containing an atomizer along with a liquid solution and a mouthpiece. The solution (often known as e‑liquid or e‑juice) is heated into an aerosol inhaled by the user. Smoking conventional cigarettes is considered a determinant factor in the development of chronic respiratory diseases, cardiovascular diseases, cancers, and reproductive system dysfunctions. Conventional smoking also causes genome damage and alteration of the transcriptome, due to the amounts of noxious substances emitted during the combustion of these products. Recently, cigarette consumers have begun to use ECIGs as a replacement or substitute practice to help them quit smoking. In addition, an increase in the use of ECIGs and similar devices by young individuals has been reported, which is unsurprising due to the unregulated distribution and sale of these products. The present review article describes and discusses the impact and the noxious effects of substances in ECIGs and other nicotine administration systems on DNA structure, gene expression profile, and epigenetic modification, focusing on the respiratory system and embryonic development.

Background: Lung cancer is the leading cause of cancer death worldwide. It has been reported that genetic and epigenetic factors play a crucial role in the onset and evolution of lung cancer. Previous reports have shown that essential transcription factors in embryonic development contribute to this pathology. Runt-related transcription factor (RUNX) proteins belong to a family of master regulators of embryonic developmental programs. Specifically, RUNX2 is the master transcription factor (TF) of osteoblastic differentiation, and it can be involved in pathological conditions such as prostate, thyroid, and lung cancer by regulating apoptosis and mesenchymal–epithelial transition processes. In this paper, we identified TALAM1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) as a genetic target of the RUNX2 TF in lung cancer and then performed functional validation of the main findings. Methods: We performed ChIP-seq analysis of tumor samples from a patient diagnosed with lung adenocarcinoma to evaluate the target genes of the RUNX2 TF. In addition, we performed shRNA-mediated knockdown of RUNX2 in this lung adenocarcinoma cell line to confirm the regulatory role of RUNX2 in TALAM1 expression. Results: We observed RUNX2 overexpression in cell lines and primary cultured lung cancer cells. Interestingly, we found that lncRNA TALAM1 was a target of RUNX2 and that RUNX2 exerted a negative regulatory effect on TALAM1 transcription.

Background: DNA methylation alterations represent a key epigenetic mechanism linking environmental exposures to disease pathogenesis. The present study aimed to identify differentially methylated genes and shared biological processes associated with lung cancer (LuCa), chronic obstructive pulmonary disease (COPD) and tobacco exposure. Methods: A comprehensive literature search was performed in PubMed to identify studies evaluating DNA methylation in LuCa, COPD and smoking-related models. A total of 117 articles were selected, including 83 studies on lung cancer, 18 on COPD and 16 on smoking exposure. Genes exhibiting statistically significant methylation changes relative to controls were extracted from each study. To provide additional support for these findings, differential methylation signatures were further evaluated using The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets. Functional and transcription factor motif enrichment analyses were subsequently conducted to identify shared biological pathways and regulatory mechanisms. Results: In total, 324 genes displaying altered methylation patterns across these conditions were identified. Seven tumor suppressor genes (CDKN2A, CDH13, MGMT, MIR137, DAPK1, RARB, and RASSF1A) consistently exhibited hypermethylation in both lung cancer and in association with smoking exposure. In addition, AHRR hypomethylation emerged as a shared epigenetic hallmark across all three conditions. TCGA-based analyses confirmed several of these methylation patterns and revealed subtype-specific methylation profiles associated with smoking history. Functional enrichment highlighted common biological processes and signaling pathways, particularly those related to transcriptional regulation, apoptosis and cancer-associated pathways. Conclusions: These results provide an integrative overview of shared DNA methylation alterations associated with smoking exposure, COPD, and lung cancer, and suggest potential DNA methylation candidates that may be relevant for future biomarker development and mechanistic studies.