miR‐96‐5p regulates wound healing by targeting BNIP3/FAK pathway

Abstract

Cutaneous wound healing is a highly orchestrated basic biological process and one of the key processes in restoring skin integrity. The role of microRNAs (miRNAs) during this process has raised numerous attention and is poorly explored. The aim of this study is to investigate the potential function of BCL2 interacting protein (BNIP3) and its target miRNA, miR-96-5p, in cutaneous wound healing. The results demonstrated that BNIP3 was significantly increased and miR-96-5p was obviously decreased during wound healing. Overexpression of BNIP3 significantly increased, while inhibition of BNIP3 decreased cell proliferation and migration of human primary keratinocytes. miR-96-5p was predicted to be a target miRNA for BNIP3 and luciferase reporter assay confirmed that miR-96-5p directly targeted the 3ʹ-untranslated region of BNIP3. Moreover, miR-96-5p overexpression significantly decreased, while miR-96-5p inhibition dramatically increased BNIP3 protein expression and focal adhesion kinase (FAK) pathway activation. Furthermore, miR-96-5p inhibited cell proliferation and migration of human primary keratinocytes. Overall, our findings suggest that miR-96-5p might be critical in the regulation of wound healing by mediating BNIP3 and FAK pathway.

Reply to Letter to the Editor: “Bnip3 as a potential target to treat airway smooth muscle remodeling in asthma?”

“…Of note, Bnip3, being a member of Bcl-2 family proteins, regulates cell death via apoptosis. Our investigations confirm recent findings by other groups that Bnip3 can modulate cell proliferation in multiple cell types (10,16,21,23). Asserting cell proliferation using additional methods (such as bromodeoxyuridine) as suggested by Beaufils and colleagues is valuable.…”

Adalimumab changes the expression profile of selected BCL‐2 family genes

“…In Wu, Cao, Zhao, and Wang's () study, whose aim was to indicate the function of the BNIP3 protein and its micro RNA (miR‐96‐5p) in wound healing, authors showed that miR‐96‐5p can be an important aspect in regulating this process by participating in a dependent pathway from BNIP3 and the Focal Adhesion Kinase proteins. Studies have shown an overexpression of the BNIP3 protein and a decrease in the corresponding miR‐96‐5 in wound healing.…”

The Role of MicroRNAs in Epidermal Barrier

“…Substantial data associated with miRNAs, either upregulated or downregulated, and keratinocyte proliferation have been reported in psoriasis. The downregulated miRNAs include miR-125b, miR-181b-5p, miR-520a, miR-194, miR-217, miR-138, miR-320b, miR-150, miR-145-5p, miR-20a-3p, miR-876-5p, miR-99a, miR-187, miR-548a-3p, miR-330, and miR-146a AKT3 [47] miR-181b-5p AKT3, TRL4 [47,48] miR-520a AKT [49] miR-320b AKT3 [50] miR-194 GRHL2 [51] miR-217 [52] miR-138 hTERT [53] miR-150 HIF-1α, VEGFA [54] miR-145-5p MLK3 [55] miR-20a-3p SFMBT1 [56] miR-876-5p ANG-1 [57] miR-99a FZD5/FZD8 [58] miR-187 CD276 [59] miR-548a-3p PPP3R1 [60] miR-330 CTNNB1 [61] miR-146a EGFR Psoriasis, cSCC [62,63] miR-96-5p BNP3 Wound healing [64] miR-181a KRAS cSCC [29] miR-99b IGF-1R Condyloma acuminatum [65] miR-203 ∆Np63 Epidermodysplasia verruciformis [66] miR-130a STK40 [79] miR-122-5p SPRY2 [80] miR-223 PTEN [81] miR-17-3p MYOT Wound healing [82] miR-126 PLK2 [83] ↑: upregulation, ↓: downregulation.…”

“…The role of miRNAs in the proliferation phase has been suggested. Downregulated miR-96-5p promotes keratinocyte proliferation by targeting the BCL2 interacting protein 3 (BNIP3) [64].…”