Epigenetic Regulation in Exposome-Induced Tumorigenesis: Emerging Roles of ncRNAs

Abstract

Environmental factors, including pollutants and lifestyle, constitute a significant role in severe, chronic pathologies with an essential societal, economic burden. The measurement of all environmental exposures and assessing their correlation with effects on individual health is defined as the exposome, which interacts with our unique characteristics such as genetics, physiology, and epigenetics. Epigenetics investigates modifications in the expression of genes that do not depend on the underlying DNA sequence. Some studies have confirmed that environmental factors may promote disease in individuals or subsequent progeny through epigenetic alterations. Variations in the epigenetic machinery cause a spectrum of different disorders since these mechanisms are more sensitive to the environment than the genome, due to the inherent reversible nature of the epigenetic landscape. Several epigenetic mechanisms, including modifications in DNA (e.g., methylation), histones, and noncoding RNAs can change genome expression under the exogenous influence. Notably, the role of long noncoding RNAs in epigenetic processes has not been well explored in the context of exposome-induced tumorigenesis. In the present review, our scope is to provide relevant evidence indicating that epigenetic alterations mediate those detrimental effects caused by exposure to environmental toxicants, focusing mainly on a multi-step regulation by diverse noncoding RNAs subtypes.

Epigenetic mechanisms of particulate matter exposure: air pollution and hazards on human health

“…The field of environmental epigenetics research has experienced a revolution due to the discovery of various ncRNA species, transforming our understanding of physiology and disease development ( Frye et al, 2021 ; Olmedo-Suárez et al, 2022 ; Rubio et al, 2023a ). ncRNAs, including miRNAs, piRNAs, and lncRNAs, play roles in biological processes by interacting with transcription factors and key regulatory proteins ( Mattick et al, 2023 ).…”

Environmental Epigenetics and Obesity

“…Specifically, air pollution is defined as the release of harmful particles into the air by one or more harmful gases. The six main air pollutants are: airborne fine particulate matter 10 microns or less in diameter (PM10) and 2.5 microns or less in diameter (PM2.5); ozone, carbon monoxide, lead, nitrogen dioxide and sulfur dioxide [20,21]. Two main types of air pollution are considered: outdoor pollution as the pollution of the ambient air, and indoor pollution as the pollution generated by domestic combustion [20].…”

“…In recent years, scientific evidence linking air pollution with obesity has been published by international groups, proposing several key biological pathways acting as a functional bridge [24,27]. It is known that the exposome (exposure to environmental compounds and factors such as stress, habits, diet, exercise, lifestyle) can affect molecular pathways and cellular processes that increase the susceptibility to develop several diseases including obesity, because of abnormal epigenetic modifications [21,28]. Early in the forties, Conrad Waddington first introduced the term "epigenetics" to describe environment-gene interactions that could not be explained by traditional Mendelian genetics [29].…”

“…Nowadays, epigenetics is defined as the study of non-genetic heritable genomic modifications that regulate gene expression without alterations in DNA sequence. Epigenetic mechanisms include DNA methylation, histone modifications and non-coding RNAs (ncRNAs), all regulating gene activity at the transcriptional, posttranscriptional, translational, and post-translational level (Figure 2) [21,30].…”

Advances of Epigenetic Biomarkers and Epigenome Editing for Early Diagnosis in Breast Cancer

“…Epigenetics is the study of heritable changes in gene expression that occur independently of alterations in DNA sequence. Epigenetic modifications affect molecular pathways during development, differentiation, and tumorigenesis, which are known to be triggered by age, diet, stress, hormones [ 38 , 39 , 40 ], as well as exposure to other environmental stimuli or factors known as exposome, as recently shown to significantly influence epigenetic modification [ 41 ]. Moreover, epigenetic alterations can be inherited through cell divisions and, in some cases, can be maintained over long periods of time or transmitted down through generations [ 42 , 43 ].…”