The Untapped Biomarker Potential of MicroRNAs for Health Risk-Benefit Analysis of Vaping vs. Smoking

Abstract

Despite the popularity of electronic cigarettes (e-cigs) among adolescent never-smokers and adult smokers seeking a less pernicious substitute for tobacco cigarettes, the long-term health impact of vaping is largely unknown. Like cigarette smoke, e-cig vapor contains harmful and potentially harmful compounds, although in fewer numbers and at substantially lower concentrations. Many of the same constituents of e-cig vapor and cigarette smoke induce epigenetic changes that can lead to the dysregulation of disease-related genes. MicroRNAs (MiRNAs) are key regulators of gene expression in health and disease states. Extensive research has shown that miRNAs play a prominent role in the regulation of genes involved in the pathogenesis of smoking-related diseases. However, the use of miRNAs for investigating the disease-causing potential of vaping has not been fully explored. This review article provides an overview of e-cigs as a highly consequential electronic nicotine delivery system, describes trends in e-cig use among adolescents and adults, and discusses the ongoing debate on the public health impact of vaping. Highlighting the significance of miRNAs in cell biology and disease, it summarizes the published and ongoing research on miRNAs in relation to gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. It identifies gaps in knowledge and priorities for future research while underscoring the need for empirical evidence that can inform the regulation of tobacco products to protect youth and promote public health.

Keywords: epigenetics; gene expression; miRNA; smoking; youth vaping.

Figure 1

Cytoscape visualization of the networks of miRNA–target interactions (disease–context) for seven dysregulated miRNAs common to e-cig users, cigarette smokers, waterpipe smokers, and dual smokers (both cigarettes and waterpipe) when compared to non-users. The interaction networks are based on the experimentally supported miRNA–target data from miRTarBase (https://mirtarbase.cuhk.edu.cn/ (accessed on 3 March 2024)) using the Human microRNA Disease Database version 4.0 (HMDD v.4.0) (http://www.cuilab.cn/hmdd (accessed on 3 March 2024)). Data are derived from ref. [110].

Figure 2

Cytoscape visualization of the networks of miRNA–target interactions (disease–context) for dysregulated miRNAs specific to e-cig users when compared to non-users. The interaction networks are based on the experimentally supported miRNA–target data from miRTarBase (https://mirtarbase.cuhk.edu.cn/ (accessed on 3 March 2024)) using the Human microRNA Disease Database version 4.0 (HMDD v.4.0) (http://www.cuilab.cn/hmdd (accessed on 3 March 2024)). Data are derived from ref. [110].

Figure 3

Differentially expressed transcripts in the oral epithelial cells of vapers and smokers compared to non-users. Numbers of upregulated and downregulated gene transcripts in vapers and smokers compared to non-users are shown. Data are derived from ref. [19].

Figure 4

Differentially expressed genes in the oral epithelial cells of vapers and smokers compared to non-users. Venn diagrams of all dysregulated genes (A) and cancer-related dysregulated genes (B) in vapers and smokers compared to non-users. DEGs = differentially expressed genes. Data are derived from ref. [19].