Association Between miR-148a and DNA Methylation Profile in Individuals Exposed to Lead (Pb)

Abstract

Experimental and epidemiologic studies have shown that lead (Pb) is able to induce epigenetic modifications, such as changes in DNA methylation profiles, in chromatin remodeling, as well as the expression of non-coding RNAs (ncRNAs). However, very little is known about the interactions between microRNAs (miRNAs) expression and DNA methylation status in individuals exposed to the metal. The aim of the present study was to investigate the impact of hsa-miR-148a expression on DNA methylation status, in 85 workers exposed to Pb. Blood and plasma lead levels (BLL and PLL, respectively) were determined by ICP-MS; expression of the miRNA-148a was quantified by RT-qPCR (TaqMan assay) and assessment of the global DNA methylation profile (by measurement of 5-methylcytosine; % 5-mC) was performed by ELISA. An inverse association was seen between miR-148a and % 5-mC DNA, as a function of BLL and PLL (β = −3.7; p = 0.071 and β = −4.1; p = 0.049, respectively) adjusted for age, BMI, smoking, and alcohol consumption. Taken together, our study provides further evidence concerning the interactions between DNA methylation profile and miR-148a, in individuals exposed to Pb.

The interaction between miRNAs and hazardous materials

“… [ 85 ] miR-148a (−) Human – – – Exposure to Pb could make an association between the methylation of DNA and miR-148a. [ 86 ] miR-155 (Up) Asian Carp 1–2 mg/L – – ERK, p38, IL-6, TNF-α, IL-1β In the carp's head kidney, miR-155 could induce inflammation in the MAPK-dependent pathway. [ 87 ] miR-155, miR-221, (Up) Human (North-Western India) – – – – Both mentioned miRNAs increased in workers exposed to Pb.…”

Extracellular vesicles in human milk

“…MiRNAs delivered inside MDEVs can be transferred into the blood circulation, to repress translation of target mRNAs in distant cells [27]. For instance, incubation of transformed and normal cells with human MDEVs resulted in downregulated expression of DNA methyltransferase 1 (DNMT1), a target gene of miR-148a [29,30] and the induction of DNA demethylation, thereby potentially regulating epigenetic modifications of target genes.…”

Metals and new approaches for biomonitoring

“…Recently, lead (Pb) bioaccumulation has received increased concern as it has been found that Pb has no safe concentration in terms of DNA modification risk in humans; thus, even low concentration Pb exposure can lead to neurological and hematological disturbance (Araujo et al, 2021). Further, recent mining disasters in Brazil and worldwide have reinforced that it is urgent to maintain metal biomonitoring programs in vulnerable areas (Bordon et al, 2023).…”