Fig. 3

LncRNAs involved in diabetic foot ulcer healing. Adequate blood supply to the damaged tissue in diabetic foot ulcers is one of the most essential wound-healing processes, which is promoted by lncRNA H19, LINC01435, MALAT1, and linc00511. LncRNA H19 supports angiogenesis through histone methylation mediated by the Enhancer of Zeste Homolog 2 (EZH2) and modulation of the HIF-1α signaling pathway. MALAT1 enhances VEGF expression, Linc00511 reduces PAQR3 and increases Twist1, and the reduction of LINC01435 leads to decreased nuclear translocation of YY1, causing knockdown of HDAC8, thereby supporting angiogenesis. To regenerate the damaged tissue and return to its normal morphology, some cells involved in wound healing need to migrate. lncRNAs H19, MALAT1, and CASC2 promote the migration of these cells. H19 does this by inhibiting miR-152-3p and increasing PTEN expression. MALAT1 supports migration through the inhibition of miR-374a-5p, and CASC2 by inhibiting miRNA 155, both enhancing HIF-1α expression and supporting cell migration and proliferation. The regeneration of ECM and extracellular space is another primary step in the wound healing, which can be related to lncRNAs URIDS, MALAT1, and H19. Reducing URIDS promotes collagen production by increasing Plod1 protein stability. MALAT1 accelerates the expression of MFGE8 through inhibition of miR-1914-3p. By recruiting SRF to the CTGF promoter region, H19 increases its expression and accelerates cell proliferation, ECM regeneration, and diabetic foot ulcer healing. To properly heal wounds, inflammation must be regulated alongside other wound healing-promoting factors. LncHAR1B supports diabetic foot ulcer healing by increasing BHLHE23, which regulates KLF4, a gene that inhibits inflammation