The biological interplay between air pollutants and miRNAs regulation in cancer

Abstract

Air pollution, especially fine particulate matter (PM2.5, with an aerodynamic diameter of less than 2.5 μm), represents a risk factor for human health. Many studies, regarding cancer onset and progression, correlated with the short and/or long exposition to PM2.5. This is mainly mediated by the ability of PM2.5 to reach the pulmonary alveoli by penetrating into the blood circulation. This review recapitulates the methodologies used to study PM2.5 in cellular models and the downstream effects on the main molecular pathways implicated in cancer. We report a set of data from the literature, that describe the involvement of miRNAs or long noncoding RNAs on the main biological processes involved in oxidative stress, inflammation, autophagy (PI3K), cell proliferation (NFkB, STAT3), and EMT (Notch, AKT, Wnt/β-catenin) pathways. microRNAs, as well as gene expression profile, responds to air pollution environment modulating some key genes involved in epigenetic modification or in key mediators of the biological processes described below. In this review, we provide some scientific evidences about the thigh correlation between miRNAs dysregulation, PM2.5 exposition, and gene pathways involved in cancer progression.

Keywords: PM2.5; lung; microRNAs (miRNAs); particulate matter; pollution.

FIGURE 1

Here, it is represented how the PM2.5 can impact on the human body. The air particulate is inhaled, reaches the pulmonary alveoli and it is transferred to the bloodstream; in this way it enters the cell metabolism, impairing it. In particular there are consequences on the miRNAs regulation, that in turns has effects on the inflammation state, cell proliferation and oxidative stress.

FIGURE 2

In this review it will explore the PM2.5 effects on cells in particular for what concerns the release of miRNAs and the biological effects exerted by themselves. The proof of concepts is based on the research of the keywords miRNAs, air particulate, lung epithelial cell (20 oct 2022) on PubMed and bioRxiv and a selection of XX articles has been included in this review. The main focus of this review was the effects of PM2.5 mainly on the modulation of miRNAs in in vitro models, by comparing different methods of stimulation.

FIGURE 3

In this figure the miRNAs activity is showed more in detail. Each miRNA has a target gene on which operates. When there is the dysregulation, and so an overexpression, of a specific miRNA there is also an impairement in the expression of its target gene. In particular we can see that this can cause autophagy inhibition, inflammation, rise of oxidative stress and, in cancer cells, increase in the migration activity.