Abstract
BackgroundMicroRNAs (miRNAs) play critical roles in corneal development and functional homeostasis. Our previous study identified miR-184 as one of the most highly expressed miRNAs in the corneal epithelium. Even though its expression level plummeted dramatically during corneal epithelial wound healing (CEWH), its precise role in mediating corneal epithelial renewal was unresolved. The present study aimed to reveal the function and mechanism of miR-184 in regulating CEWH.MethodsQuantitative RT-PCR analysis characterized the miR-184 expression pattern during CEWH in mice. Ectopic miR-184 injection determined its effect on this process in vivo. We evaluated the effects of miR-184 and its target genes on the proliferation, cell cycle, and migration of human corneal epithelial cells (HCECs) using MTS, flow cytometry, and wound-healing assay, respectively. Bioinformatic analysis, in conjunction with gene microarray analysis and cell-based luciferase assays, pinpointed gene targets of miR-184 contributing to CEWH.ResultsMiR-184 underwent marked downregulation during mouse CEWH. Ectopic miR-184 overexpression delayed this process in mice. Furthermore, miR-184 transfection into HCECs significantly inhibited cell proliferation, cell cycle progression, and cell migration. MiR-184 directly targeted CDC25A, CARM1, and LASP1, and downregulated their expression in HCECs. CARM1 downregulation inhibited both HCEC proliferation and migration, whereas a decrease in LASP1 gene expression only inhibited migration.ConclusionsOur results demonstrate that miR-184 inhibits corneal epithelial cell proliferation and migration via targeting CDC25A, CARM1, and LASP1, suggesting it acts as a negative modulator during CEWH. Therefore, identifying strategies to suppress miR-184 expression levels has the potential to promote CEWH.
Highlights
MicroRNAs play critical roles in corneal development and functional homeostasis
MiR-184 Downregulation during murine corneal epithelial wound healing We previously found that only miR-204 and miR-184 were dramatically downregulated over 200-fold during the mouse CEWH process using NanoString nCounter technology [12]
Restoration of miR-184 delays corneal epithelial wound healing in vivo To ascertain that such a decline of miR-184 is requisite for CEWH, we determined if miR-184 ectopic expression would delay the wound healing response
Summary
MicroRNAs (miRNAs) play critical roles in corneal development and functional homeostasis. If severe injury or infection disrupts this renewal process, pathogenic infiltration into the stroma can occur and disrupt its organization and makeup Such changes can lead to tissue swelling and opacification, followed by losses in visual acuity [7]. In order to improve the treatment of sight compromised by epithelial wounds in a clinical setting, numerous studies are underway to clarify how these mediators modulate gene expression during wound healing [8, 9]. Through these endeavors, it may be possible to identify novel drug targets for reducing the risk of corneal infection and complications, possibly requiring transplantation surgery
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