2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) and Polychlorinated Biphenyl Coexposure Alters the Expression Profile of MicroRNAs in the Liver Associated with Atherosclerosis

Abstract

MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that exist as complex mixtures in vivo. When humans are simultaneously exposed to these compounds, the development of atherosclerosis is known to be enhanced. However, the roles of miRNA in TCDD- and PCB-induced atherosclerosis are largely unknown. Therefore, the present study is aimed at elucidating the possible dysregulation of miRNAs in atherogenesis induced by coexposure to TCDD and PCBs. Eight-week-old male ApoE-/- mice were coexposed to TCDD (15 μg/kg) and Aroclor1254 (55 mg/kg, a representative mixture of PCBs) by intraperitoneal injection four times over a 6-week period. Microarray analysis of miRNAs and mRNAs in the liver of ApoE-/- mice with or without TCDD and Aroclor1254 coexposure was performed. We discovered that 68 miRNAs and 1312 mRNAs exhibited significant expression changes in response to TCDD and PCB coexposure and revealed that both changed miRNAs and mRNAs are involved in cardiovascular disease processes. An integrated miRNA-mRNA approach indicated that miRNA-26a-5p, miRNA-193a-3p, and miRNA-30c-5p participated in specific TCDD and Aroclor1254 coresponsive networks which are relevant to the cardiovascular system development and function network. Furthermore, our results also indicated that miRNA-130a-3p and miRNA-376a-3p were novel players in the regulation of TCDD- and Aroclor1254-induced atherosclerosis pathways. In summary, our finding provided new insights into the mechanism of atherosclerosis in response to TCDD and PCB coexposure.

Female‐to‐male differential transcription patterns of miRNA‐mRNA networks in the livers of dioxin‐exposed mice

“…In line with this, the downregulation of Mir122 by TCDD or by Streptozotocin, a hepatocellular carcinoma-induced chemical, was also reported. 88,89,95 This was also confirmed by Moffat et al 90 using Ahr À/À and WT Ahr +/+ mice exposed to TCDD. However, an opposite scenario concerning Mir290A expression was reported during drug-induced liver injury.…”

“…The involvement of liver miRNAs in the regulation of genes expression as a response to dioxin exposure has previously investigated in over narrow scale. [88][89][90] The current study demonstrates that the exposure of mice to TCDD results in significant modifications in the expression profile of certain liver miRNAs. The transcripts of two classes of miRNAs each containing 19 types, were quantified as a function of TCDD exposure.…”

“…[82][83][84][85][86][87] The involvement of liver miRNAs in the regulation of genes expression as a response to dioxin exposure was previous investigated over a restricted scale. [88][89][90] Thus, the current study was conducted to present a wider overview on the transcriptional pattern of miRNAs in the mouse liver after exposure to TCDD to determine the potential regulatory effects these miRNAs on the target mRNAs. For this purpose, the relative abundances of 38 miRNAs transcripts, directly or indirectly involved in hepatopathology, were quantified in the liver of female and male BALB/c mice after exposure to a single dose of TCDD.…”

“…The involvement of liver miRNAs in the regulation of genes expression as a response to dioxin exposure was previous investigated over a restricted scale 88–90 . Thus, the current study was conducted to present a wider overview on the transcriptional pattern of miRNAs in the mouse liver after exposure to TCDD to determine the potential regulatory effects these miRNAs on the target mRNAs.…”

Evaluation of Early Biomarkers of Atherosclerosis Associated with Polychlorinated Biphenyl Exposure: An in Vitro and in Vivo Study

“…ncRNAs profile changes driven by PCBs have been reported ( Chen et al. 2020 ; Shan et al. 2020 ; Wahlang et al.…”