Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30785991http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

DNA methylation is a key epigenetic modification involved in various biological processes and diseases. Corneal epithelial wound healing (CEWH) is essential for restoring corneal integrity and transparency after injury. However, the role of DNA methylation in CEWH remains elusive. Here, we investigate the function and underlying mechanism of DNA methylation in regulating CEWH.

Methods

Dot blots and global methylation assays determined DNA methylation levels during CEWH. Quantitative RT-PCR and Western blot analysis examined the expression of DNA methyltransferases (DNMTs), cyclin-dependent kinase inhibitor 2B (CDKN2B), and miR-200a during CEWH, respectively. MTS assays and flow cytometry were used to analyze human corneal epithelial cell (HCEC) proliferation and cell cycle, respectively. The in vitro scratch wound assay assessed HCEC migration and an in vivo murine corneal epithelial debridement model evaluated wound healing. Using bisulfite sequencing PCR, we determined the DNA methylation status of the candidate genes. Transfection of miR-200a mimic or inhibitor assessed the function of miR-200a in HCECs. Rescue experiments were performed to clarify the correlation between DNMT1 and miR-200a/CDKN2B during CEWH.

Results

DNMT1 and DNMT3B expression was significantly upregulated during CEWH, resulting in a significant global DNA hypermethylation. DNMT1 downregulation dramatically delayed CEWH in vivo, and suppressed HCEC proliferation and migration. MiR-200a inhibited HCEC migration. Furthermore, miR-200a and CDKN2B were identified as molecular targets of DNA methylation and as having a causal connection with DNMT1.

Conclusions

DNMT1-mediated DNA hypermethylation can enhance the process of CEWH by directly targeting miR-200a and CDKN2B. This insight pinpoints novel potential drug targets for promoting CEWH."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.org/dc/terms/identifier"doi:10.1167/iovs.18-25443"xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Dong J."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Luo G."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Yang S."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Jing X."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Yan D."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Peng D."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/author"Reinach P.S."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/pages"650-660"xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/title"DNA Methylation Regulates Corneal Epithelial Wound Healing by Targeting miR-200a and CDKN2B."xsd:string
http://purl.uniprot.org/citations/30785991http://purl.uniprot.org/core/volume"60"xsd:string
http://purl.uniprot.org/citations/30785991http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/30785991
http://purl.uniprot.org/citations/30785991http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/30785991
http://purl.uniprot.org/uniprot/#_O54846-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/#_Q3UNM8-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/#_P55271-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/#_Q549R4-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/#_Q9QUJ3-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/#_Q9QUP0-mappedCitation-30785991http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/30785991
http://purl.uniprot.org/uniprot/Q9QUP0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/30785991
▶