MicroRNAs as potential signatures of environmental exposure or effect: a systematic review

Abstract

Background: The exposome encompasses all life-course environmental exposures from the prenatal period onward that influence health. MicroRNAs (miRNAs) are interesting entities within this concept as markers and causation of disease. MicroRNAs are short oligonucleotide sequences that can interact with several mRNA targets.

Objectives: We reviewed the current state of the field on the potential of using miRNAs as biomarkers for environmental exposure. We investigated miRNA signatures in response to all types of environmental exposure to which a human can be exposed, including cigarette smoke, air pollution, nanoparticles, and diverse chemicals; and we examined the health conditions for which the identified miRNAs have been reported (i.e., cardiovascular disease, cancer, and diabetes).

Methods: We searched the PubMed and ScienceDirect databases to identify relevant studies.

Results: For all exposures incorporated in this review, 27 miRNAs were differentially expressed in at least two independent studies. miRNAs that had expression alterations associated with smoking observed in multiple studies are miR-21, miR-34b, miR-125b, miR-146a, miR-223, and miR-340; and those miRNAs that were observed in multiple air pollution studies are miR-9, miR-10b, miR-21, miR-128, miR-143, miR-155, miR-222, miR-223, and miR-338. We found little overlap among in vitro, in vivo, and human studies between miRNAs and exposure. Here, we report on disease associations for those miRNAs identified in multiple studies on exposure.

Conclusions: miRNA changes may be sensitive indicators of the effects of acute and chronic environmental exposure. Therefore, miRNAs are valuable novel biomarkers for exposure. Further studies should elucidate the role of the mediation effect of miRNA between exposures and effect through all stages of life to provide a more accurate assessment of the consequences of miRNA changes.

Figure 1

Overview of miRNA biogenesis. The canonical maturation of a miRNA includes the production of the primary miRNA transcript (pri-miRNA) by RNA polymerase II or III (Pol II/III) and cleavage of the pri-miRNA by the microprocessor complex Drosha–DGCR8 (Pasha) in the nucleus. The resulting precursor hairpin, the pre-miRNA, is exported from the nucleus by Exportin-5–Ran-GTP. In the cytoplasm, the RNase Dicer in complex with the double-stranded RNA-binding protein TRBP cleaves the pre-miRNA hairpin to its mature length. The functional strand of the mature miRNA is loaded together with Argonaute (Ago2) proteins into the RNA-induced silencing complex (RISC), where it guides RISC to silence target mRNAs through mRNA cleavage, translational repression, or deadenylation, whereas the passenger strand (black) is degraded.

Figure 2

Flowchart of included studies.

Figure 3

Venn diagram displaying common and distinct microRNAs associated with smoking in in vitro, in vivo, and human studies. miRNAs in bold type were identified in more than one study included in this meta-analysis.

Figure 4

Venn diagram displaying common and distinct microRNAs associated with air pollution exposure in in vitro and human studies. miRNAs in bold type were identified in more than one study included in this meta-analysis.

Figure 5

Venn diagram displaying common and distinct microRNAs associated with arsenic exposure in in vitro and human studies. miRNAs in bold type were identified in more than one study included in this meta-analysis.