It seems logical that in diabetic foot ulcers elevated levels of miR-221-3p contribute to wound healing (through its effects on homeodomain-interacting protein kinase 2 (HIPK2) (Yu et al., 2022) and the AKT/eNOS (Yu et al., 2020b) and DYRK1A/STAT3 signaling pathways (Hu et al., 2024), whereas in DR, conversely, miR-221-3p promotes microvascular dysfunction (by affecting tissue inhibitor of metalloproteinase 3 (TIMP3) (Wang et al., 2020a)), with its serum level positively correlating with VEGF levels and disease progression (Liu et al., 2018; Zhao & Pan, 2023). Here, HIPK2 is linked to diabetic foot.