Mir126a, an endothelial-specific microRNA, is known to be involved in multiple biological processes. It has been implicated in maintaining vascular integrity and is essential for lymphatic system development, modulating Vegfr signaling [4]. It also participates in various regulatory pathways related to cell quiescence, self-renewal, and may have a role in gene expression regulation through post-transcriptional repression [2,3].

In a study on chronic myelogenous leukemia (CML), conditional knockout of Mir126a in endothelial cells (ECs) and/or leukemia stem cells (LSCs) in mouse models showed that miR-126 supported the quiescence, self-renewal, and engraftment capacity of CML LSCs. Inhibition of BCR-ABL by tyrosine kinase inhibitors (TKIs) increased endogenous miR-126 levels, enhancing LSC quiescence and persistence. However, Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor, enhanced the in vivo anti-leukemic effects of TKI treatment and diminished LSC leukemia-initiating capacity [2]. In another study, aging in mice was associated with downregulation of miR126a in the uterus, along with changes in the Pi3k/Akt1/mTor signaling pathway. The senolytic drug combination of dasatinib plus quercetin (D + Q) had effects on related gene and miRNA expressions, suggesting a possible role of miR126a in uterine aging and fibrosis [1].

In conclusion, Mir126a is crucial for lymphatic development and plays important roles in diseases such as chronic myelogenous leukemia and uterine-related age-associated dysfunctions. The use of gene knockout mouse models, especially in the context of CML and uterine aging studies, has provided valuable insights into the function of Mir126a in these specific biological processes and disease conditions.