MicroRNA Let‐7b inhibits keratinocyte migration in cutaneous wound healing by targeting IGF2BP2

Abstract

Wound healing is a complex process which involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family, let-7b, has been expressed in mammalian skin, but its exact role in keratinocyte migration is still not in knowledge. Here, we showed that let-7b regulates keratinocyte migration by targeting the insulin-like growth factor IGF2BP2. Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during wound healing in wild-type mice, which led us to construct the transgenic mice with overexpression of let-7b in skin. The re-epithelialization of epidermis of let-7b transgenic mice was reduced during wound healing. Using bioinformatics prediction software and a reporter gene assay, we found that IGF2BP2 was a target of let-7b, which contributes to keratinocyte migration. Introduction of an expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency, which confirms that IGF2BP2 is an important target for let-7b regulation. Our findings suggest that let-7b significantly delayed the re-epithelialization possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during skin wound healing.

MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated ERK signaling in psoriasis

“…Recent study demonstrated that let-7b stimulates differentiation and prevents metaplasia by regulating HNF6 expression in pancreatic acinar cells [ 14 ]. It is also becoming increasingly recognized that let-7b plays an important role in hair growth [ 15 , 16 ], cutaneous wound healing [ 17 ] and skin disease [ 18 ]. Recently, it was found that let-7b inhibits keratinocyte migration through targeting IGF2BP2 [ 17 ].…”

“…It is also becoming increasingly recognized that let-7b plays an important role in hair growth [ 15 , 16 ], cutaneous wound healing [ 17 ] and skin disease [ 18 ]. Recently, it was found that let-7b inhibits keratinocyte migration through targeting IGF2BP2 [ 17 ]. As well as, let-7b has been also implicated in other malignacies e.g.…”

Identification and functional analysis of inflammation‐related miRNAs in skin wound repair

“…Furthermore, we have shown that miR-142 is required for neutrophils to clear S. aureus infected-skin wound sites (Tanaka et al, 2017). Mice with Let-7b overexpression exhibit a delay in re-epithelialization at skin wound sites (Wu et al, 2017).…”

Identification of Specific miRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression of miRNA-129-2-3p Accelerates Diabetic Wound Healing

“…miR-126 overexpression has been shown to rescue the diabetes-induced impairment of phagocytosis of apoptotic cardiomyocytes (13). In addition, Let-7b was revealed to inhibit keratinocyte migration in cutaneous wound healing (14). Moreover, reports have described that the topical application of miR-132 mimic mixed with pluronic F-127 gel in chronic wounds promotes reepithelialization (15) and that miR-27b rescues impaired BM-derived angiogenic cell function and improved wound healing in type 2 diabetic mice (16).…”