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Salivary miRNA profiles in relationship with occupational stress

ABSTRACT: Work-related stress in police officers has been recognized as a risk factor for mental and physical illness, compromising work performance and public safety. While genetic, individual and environmental factors may contribute to stress, basic pathophysiological mechanisms are still not completely understood. Previous studies have shown the potential of microRNAs (miRNAs) as biomarkers and/or mediator for stress responses. In this study, we aimed at identifying possible dysregulation of salivary miRNAs associated with work-related stress in police officers. The study was conducted in a cohort composed of police officers in service at the mobile unit of Genoa in 2009, whose response to occupational stress has been continuously monitored since 2009 using the Demand-Control and the Effort-Reward Imbalance models. 113 male police officers in service in 2022 were recruited and divided in three groups according to their response to stress (low, intermediate and high stress response). miRNAs were extracted from saliva samples and analyzed by small RNA sequencing followed by an integrated bioinformatics/biostatistics analysis. The high stress response group was characterized by 18 differentially expressed miRNAs compared with the low stress response group, with four miRNAs (miR-10400-5p, miR-1290, miR-6074-5p, and miR-9902) at higher levels and fourteen miRNAs (miR-203a-3p, miR-7-5p, miR-143-3p, miR-181a-5p, miR-142-5p, miR-223-5p, let-7f-5p, let-7g-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-26a-5p, miR-142-3p, and miR-21-5p) at lower levels. We also discovered sets of miRNAs that exhibited dynamic expression changes in response to intermediate and low stress. Functional enrichment analysis identified processes related to apoptosis, cellular response to stress, negative regulation of gene expression, responses to abiotic stimuli, positive regulation of catabolism as commonly regulated by the modulated miRNAs. Work-related stress response was associated with specific salivary miRNA expression patterns, with a general decrease of miRNA levels in the highly distressed police officers. These results suggest salivary miRNA profiling as a non-invasive and useful biomarker of stress and further characterize the link between chronic psychosocial stress and cellular and behavioral response mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE285846 | GEO | 2025/01/04

REPOSITORIES: GEO

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Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.

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Salivary miRNA profiles in relationship with occupational stress

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