MicroRNA-126: A key regulator of angiogenesis, inflammation, and tumorigenesis — Exploring its multifaceted functions in vascular health and cancer

MicroRNAs (miRNAs) are small, noncoding RNA molecules (20 to 24 nucleotides) that serve as essential regulators of gene expression through post-transcriptional mechanisms. Among these miRNAs, microRNA-126 (miR-126) has emerged as a key player in angiogenesis, vascular biology, inflammation, and fibrosis. Encoded in the intron of the epidermal growth factor-like domain 7 (EGFL7) gene, miR-126 undergoes canonical biogenesis and forms complexes that repress target messenger RNAs (mRNAs) by binding to complementary sequences in their 3′-untranslated regions (UTRs). MiR-126 have two distinct mature subtypes, namely miR-126-3p and miR-126-5p. The key miR-126 targets include factors such as SPRED1, PIK3R2, PTEN, VEGF, EGFL7, CXCL12, and others. Importantly, changes in miR-126 expression are associated with numerous diseases affecting vascular functions, which highlights its therapeutic potential to improve neovascularisation and underlines its importance as a biomarker for assessing disease risk. This review integrates the current understanding of miR-126 mechanisms of action, its implications in vascular pathologies, and therapeutic strategies, highlighting its importance in cardiovascular health and cancer biology.