MicroRNA profile for health risk assessment: Environmental exposure to persistent organic pollutants strongly affects the human blood microRNA machinery

Abstract

Persistent organic pollutants (POPs) are synthetic chemical substances that accumulate in our environment. POPs such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) have been classified as carcinogenic to humans and animals. Due to their resistance to biodegradation humans are still exposed to these compounds worldwide. We aim to evaluate the miRNA and transcriptomic response of a human population exposed to POPs. The miRNA and transcriptomic response was measured in blood of healthy subjects by microarray technology and associated with the serum concentrations of six PCB congeners, DDE (a common DDT metabolite), and HCB. A total of 93 miRNA levels appeared significantly associated with the POP-exposure (FDR < 0.05). The miRNA profile includes four tumor suppressor miRNAs, namely miR-193a-3p, miR-152, miR-31-5p and miR-34a-5p. Integration of the miRNA profile with the transcriptome profile suggests an interaction with oncogenes such as MYC, CCND1, BCL2 and VEGFA. We have shown that exposure to POPs is associated with human miRNA and transcriptomic responses. The identified miRNAs and target genes are related to various types of cancer and involved in relevant signaling pathways like wnt and p53. Therefore, these miRNAs may have great potential to contribute to biomarker-based environmental health risk assessment.

miR‑34a regulates the chemosensitivity of retinoblastoma cells via modulation of MAGE‑A/p53 signaling

“…Accumulating evidence has demonstrated that aberrant expression of miR-34a regulates the progression of various neoplasms (25), including glioma (26), breast cancer (27,28), cervical cancer (29), cholangiocarcinoma (30) and multiple myeloma (31). The results of the present study demonstrated that the expression level of miR-34a was reduced in RB tissues compared with that in paracarcinoma tissues (P<0.05).…”

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution

“…Several studies have thus highlighted the impact of environmental exposure on gene expression profiles, (van Leeuwen et al, 2006) DNAmethylation patterns, (Georgiadis et al, 2016) and p53 status (Intarasunanont et al, 2012). More recently, environmental exposureinduced alterations in microRNA (miRNA) levels have been described (Krauskopf et al, 2017a). These small non-coding RNAs are involved in the posttranscriptional regulation of gene expression, and consequently are involved in virtually all cellular processes (Bartel, 2009).…”

The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome

“…Following the frequent inclusion of epigenetics as a parameter in environmental epidemiology studies, numerous reports have been made in recent years associating alterations in DNA methylation with various environmental factors, including biological agents, dietary habits, and air pollution (Ambatipudi et al 2016;Barouki et al 2018;de FC Lichtenfels et al 2018;Degli Esposti et al 2017;Fasanelli et al 2019;Feil and Fraga 2012;Hattori and Ushijima 2016;Herceg et al 2018;Martin and Fry 2018;Perrier et al 2019;Woo et al 2018). Similarly, many reports indicate that microRNA (miRNA) profiles are responsive to various environmental exposures, including air pollution ; Espín-Pérez et al (2018), both epidemiological studies], nanoparticles [Brzóska et al (2019), utilizing human liver cells], endocrine disruptors, such as bisphenol A (BPA) [Chou et al (2017), using human endometrial cells, and Martínez-Ibarra et al (2019), using human blood samples], and dichlorodiphenyltrichloroethane (DDT) [Krauskopf et al (2017), using human blood]. Long noncoding RNAs (lncRNAs), although still a relatively new area of research, have been reported to be associated with levels of phthalates in first trimester urine of pregnant women (LaRocca et al 2014), benzene in seven exposed individuals (Bai et al 2014b), and occupational exposure to cadmium (Zhou et al 2015) and to be responsive to developmental exposure to BPA in mice (Kumamoto and Oshio 2013) and to certain heavy metals in in vitro (Tani et al 2014;Zhou et al 2015) and in vivo experimental systems (Zhou et al 2015).…”