Circ_0084443 Inhibits Wound Healing Via Repressing Keratinocyte Migration Through Targeting the miR-17-3p/FOXO4 Axis

2021 ◽  
Author(s):  
Zongliang He ◽  
Xing Xu
Keyword(s):  
Wound Healing ◽  
Keratinocyte Migration

scholarly journals EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis

2017 ◽  
Vol 214 (10) ◽  
pp. 2889-2900 ◽  
Author(s):  
Gopinath M. Sundaram ◽  
Hisyam M. Ismail ◽  
Mohsin Bashir ◽  
Manish Muhuri ◽  
Candida Vaz ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Prognostic Significance ◽  
Competitive Inhibitor ◽  
Molecular Switch ◽  
Extracellular Signal Regulated Kinase ◽  
Keratinocyte Migration ◽  
Extracellular Signal ◽  
Single Transcript ◽  
Kinase Phosphorylation

Epithelial carcinomas are well known to activate a prolonged wound-healing program that promotes malignant transformation. Wound closure requires the activation of keratinocyte migration via a dual-state molecular switch. This switch involves production of either the anti-migratory microRNA miR-198 or the pro-migratory follistatin-like 1 (FSTL1) protein from a single transcript; miR-198 expression in healthy skin is down-regulated in favor of FSTL1 upon wounding, which enhances keratinocyte migration and promotes re-epithelialization. Here, we reveal a defective molecular switch in head and neck squamous cell carcinoma (HNSCC). This defect shuts off miR-198 expression in favor of sustained FSTL1 translation, driving metastasis through dual parallel pathways involving DIAPH1 and FSTL1. DIAPH1, a miR-198 target, enhances directional migration through sequestration of Arpin, a competitive inhibitor of Arp2/3 complex. FSTL1 blocks Wnt7a-mediated repression of extracellular signal–regulated kinase phosphorylation, enabling production of MMP9, which degrades the extracellular matrix and facilitates metastasis. The prognostic significance of the FSTL1-DIAPH1 gene pair makes it an attractive target for therapeutic intervention.

scholarly journals MicroRNA-200b/c-3p regulate epithelial plasticity and inhibit cutaneous wound healing by modulating TGF-β-mediated RAC1 signaling

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Huiyi Tang ◽  
Xueer Wang ◽  
Min Zhang ◽  
Yuan Yan ◽  
Simin Huang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Luciferase Reporter ◽  
Skin Wounds ◽  
Cutaneous Wound Healing ◽  
Mirna Regulation ◽  
Cutaneous Wound ◽  
Cutaneous Wounds ◽  
Keratinocyte Migration ◽  
Epithelial Plasticity ◽  
Tgf Β1

Abstract Cutaneous wound healing is pivotal for human skin to regain barrier function against pathogens. MicroRNAs (miRNAs) have been found to play regulatory roles in wound healing. However, the mechanism of miRNA regulation remains largely unknown. In this study, we focused on microRNA-200b/c-3p (miR-200b/c-3p) whose expression was abundant in intact epidermis, but dramatically decreased in skin wounds. In silico prediction identified RAC1 as a potential miR-200b/c-3p target. Luciferase reporter assay confirmed that miR-200b/c-p repressed RAC1 by direct targeting to its mRNA 3′UTR. Consistently, miR-200b/c-3p expression was discordantly related to RAC1 protein level during wound healing. Forced miR-200b/c-3p expression repressed RAC1 and inhibited keratinocyte migration as well as re-epithelialization in a mouse back skin full-thickness wound healing model. Mechanistically, miR-200b/c-3p modulated RAC1 to inhibit cell migration by repressing lamellipodia formation and intercellular adhesion dissolution in keratinocytes. Furthermore, we found that TGF-β1, which was highly expressed in skin wounds, contributed to the downregulation of miR-200b/c-3p in wound edge keratinocytes. Taken together, miR-200b/c-3p-mediated RAC1 repression inhibited keratinocyte migration to delay re-epithelialization. TGF-β1 induction attenuated miR-200b/c-3p regulation of RAC1 signaling in cutaneous wounds and the repression of miR-200b/c-3p accelerated keratinocyte migration to promote wound healing. Our data provide new insight into how miR-200b/c-3p affects keratinocyte migration and highlight the potential of miR-200b/c-3p targeting for accelerating wound healing.

scholarly journals 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor

2014 ◽  
Vol 205 (4) ◽  
pp. 2054OIA98
Author(s):  
Min Liu ◽  
Kazuko Saeki ◽  
Takehiko Matsunobu ◽  
Toshiaki Okuno ◽  
Tomoaki Koga ◽  
...  
Keyword(s):  
Wound Healing ◽  
Keratinocyte Migration
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