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

Abstract

Wound healing is a complex process involves proliferation and migration of keratinocyte for closure of epidermal injuries. A member of microRNA family let-7b, have 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. By 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, 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.

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