MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and jointly sustain NF-κB activity in mercury toxicity

Abstract

Occupational and environmental exposure to mercury is a public health concern worldwide. Although the altered epigenetic regulatory features, such as microRNA, have been associated with mercury exposure, the underlying molecular mechanism is not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR-486 are novel diagnostic biomarkers of occupational mercury poisoning, and to explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT-qPCR assays and receiver operating characteristics curve analyses were conducted to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of occupational mercury poisoning. Dual-luciferase assay was applied to confirm the target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein expression levels. Cell apoptosis was determined by flow cytometry. Results show that miR-92a and miR-486 expression levels were up-regulated in workers exposed to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial role in mercury toxicity by jointly activating the NF-κB signaling pathway via targeting KLF4 and Cezanne, respectively.

Antagonistic effect of selenium on mercuric chloride in the central immune organs of chickens: The role of microRNA‐183/135b‐FOXO1/TXNIP/NLRP3 inflammasome axis

“…Emerging evidences suggested that dysregulated miRNAs are involved in the biotoxicity of Hg. 19 In addition, several recent studies have highlighted the sensitivity of FOXO1 expression to miRNA regulation. 21,52,53 This prompted us to explore whether the inhibitory effect of HgCl 2 on FOXO1 was mediated by miRNAs.…”

“…An increasing number of studies have identified the regulation of target genes by miRNAs are involved in the tissue toxicity caused by heavy metals 18 . Ding et al found that Hg exposure interfered with the human miRNA expression profile and suggested miR‐92a and miR‐486 as diagnostic biomarkers for Hg intoxication 19 . Several studies have reported that miRNAs involved in various physiological activities by targeting FOXO1.…”

“…18 Ding et al found that Hg exposure interfered with the human miRNA expression profile and suggested miR-92a and miR-486 as diagnostic biomarkers for Hg intoxication. 19 Several studies have reported that miRNAs involved in various physiological activities by targeting FOXO1. Mmu-miR-150 has been reported to regulate programs CD8 + T cell differentiation by mediating FOXO1.…”

Impact of Air Pollution in Airway Diseases: Role of the Epithelial Cells (Cell Models and Biomarkers)

“…HUVEC cell lines were used to demonstrate the effects of Hg on the expression of miR-92a and miR-486; the parallel analysis of the plasma of workers exposed to Hg confirms the increase in the expression of the same microRNAs. This demonstrates how through integrated approaches of in vitro/in vivo studies, it is possible to demonstrate an aberrant alteration of molecular biomarkers that interfere in the activation pathways of inflammatory mechanisms involving NF-κB and the expression of COX-2 altering the physiological apoptotic processes [ 190 ].…”

Toxic-Metal-Induced Alteration in miRNA Expression Profile as a Proposed Mechanism for Disease Development

“…Inorganic Hg (HgCl 2 , etc.) has a lower toxic potential and is absorbed less through skin but can still be absorbed via the gastrointestinal tract following ingestion [114].…”