MiR-100-5p as a biomarker in hand-arm vibration disease: Mediating pathogenesis through angiogenesis suppression

Hand-arm vibration disease (HAVD), also known as occupational Raynaud's disease, is an occupational disease that can cause injuries to the microcirculation in the fingertips, might leading to severe vascular and neurological damage. While HAVD has been defined as a peripheral vascular injury disorders, its comprehensive disease mechanisms-spanning molecular drivers, pathophysiological cascades, and clinically actionable biomarkers remain substantially unelucidated. Our study has used miRNA Sequencing (miRNA-seq) to investigate the differential expression of miRNAs in HAVD patients compared to workers exposed to hand-transmitted vibration. In vitro, human umbilical vein endothelial cells (HUVECs) have been utilized to explore the role of miR-100-5p in endothelial cell dysfunction. Our results reveal that 36 miRNAs were upregulated and 2 miRNAs were downregulated in HAVD patients. Notably, miR-100-5p and miR-4735-5p exhibited the most significant differential expression.The area under the curve (AUC) for miR-100-5p in distinguishing hand-transmitted vibration-exposed workers from healthy individuals was 0.9906, while its AUC for identifying HAVD was 0.9922. The combination of those two miRNAs as the diagnostic marker of HAVD showed great potential has higher AUC, with high sensitivity, and specificity. Furthermore, miR-100-5p might mediate the pathology of HAVD by inhibiting vascular cell angiogenesis via VEGFA/VEGFR pathway, which could be regulated by decreased TRIB2 expression and inhibition of the p38 MAPK signaling pathway.

Angiogenesis; Biomarker; Early diagnosis; Hand-arm vibration disease (HAVD); Peripheral vascular injuries; Raynaud's phenomenon (RP); TRIB2; miR-100-5p.