title: Human Corneal MicroRNA Expression Profile in Fungal Keratitis.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are small, stable, noncoding RNA molecules with regulatory function and marked tissue specificity that posttranscriptionally regulate gene expression. However, their role in fungal keratitis remains unknown. The purpose of this study was to identify the miRNA profile and its regulatory role in fungal keratitis.
  
  
  METHODS
  Normal donor (n = 3) and fungal keratitis (n = 5) corneas were pooled separately, and small RNA deep sequencing was performed using a sequencing platform. A bioinformatics approach was applied to identify differentially-expressed miRNAs and their targets, and select miRNAs were validated by real-time quantitative PCR (qPCR). The regulatory functions of miRNAs were predicted by combining miRNA target genes and pathway analysis. The mRNA expression levels of select target genes were further analyzed by qPCR.
  
  
  RESULTS
  By deep sequencing, 75 miRNAs were identified as differentially expressed with fold change greater than 2 and probability score greater than 0.9 in fungal keratitis corneas. The highly dysregulated miRNAs (miR-511-5p, miR-142-3p, miR-155-5p, and miR-451a) may regulate wound healing as they were predicted to specifically target wound inflammatory genes. Moreover, the increased expression of miR-451a in keratitis correlated with reduced expression of its target, macrophage migration inhibitory factor, suggesting possible regulatory functions.
  
  
  CONCLUSIONS
  This is, to our knowledge, the first report on comprehensive human corneal miRNA expression profile in fungal keratitis. Several miRNAs with high expression in fungal keratitis point toward their potential role in regulation of pathogenesis. Further insights in understanding their role in corneal wound inflammation may help design new therapeutic strategies.
authors.affiliation: Department of Microbiology Aravind Medical Research Foundation, Madurai, India.
authors.forename: Hemadevi
authors.initials: H
authors.lastname: Boomiraj
authors.affiliation: Department of Microbiology Aravind Medical Research Foundation, Madurai, India.
authors.forename: Vidyarani
authors.initials: V
authors.lastname: Mohankumar
authors.affiliation: Department of Microbiology Aravind Medical Research Foundation, Madurai, India.
authors.forename: Prajna
authors.initials: P
authors.lastname: Lalitha
authors.affiliation: Department of Bioinformatics, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Bharanidharan
authors.initials: B
authors.lastname: Devarajan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001228:Aspergillosis / Q000235:genetics*; D001231:Aspergillus flavus / Q000302:isolation & purification; D003315:Cornea / Q000378:metabolism; D015821:Eye Infections, Fungal / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007634:Keratitis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D035683:MicroRNAs