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Novel role of PELI 3 as a potential biomarker for Sjogren's syndrome related dry eyes
Author(s) -
Pilson Q.,
Ni Gabhann J.,
Murphy C.C.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.1512
Subject(s) - microrna , microarray , microarray analysis techniques , messenger rna , hela , pathogenesis , gene expression , biomarker , gene , fold change , biology , immunology , microbiology and biotechnology , medicine , in vitro , genetics
Purpose In Sjogren's syndrome ( SS ) related dry eyes ( SS ‐ KCS ), reduced aqueous tear production and tear hyperosmolarity leads to inflammatory damage to the ocular surface. micro RNA s (miR) are known to alter the expression of cytokines, which plays an important role in the pathogenesis and progression of SS . The aim of this study was to isolate miRs and mRNA from conjunctival epithelial cells ( CEC ) of patients with primary SS ( pSS ) to identify potential biomarkers that might aid diagnosis and future therapy in pSS . Methods Confirmed SS ‐ KCS and healthy controls were recruited to this study. mRNA isolated from conjunctival impression cytology was sent for miR and mRNA microarray. Bioinformatic analysis was performed to identify predicted targets and comparison was made with the mRNA microarray data. Validation experiments were performed in HeLa cells following transfection with selected miR mimics and predicted genes were detected using qPCR . Results miR and mRNA microarray found 32 differentially expressed novel miRs and 136 differentially expressed genes in pSS patients compared to healthy controls. Following bioinformatic analysis, novel miR‐A was chosen for further analysis. miR‐A was significantly increased in pSS (p = 0.0079) and bioinformatics suggested Pellino3 ( PELI 3), a negative regulator of inflammatory cytokines, as a predicted target. The mRNA microarray showed a decrease in PELI 3 in pSS patients compared to healthy controls (p = 0.0731). Overexpression of miR‐A mimic in HeLa cells resulted in decreased expression of PELI 3, suggesting that it is a direct target for miR‐A. Conclusions We have identified differentially expressed miRs and gene targets from CEC in pSS . PELI 3, a potential target of novel miR‐A which is over expressed in pSS , is a negative regulator of cytokines that might have biomarker and therapeutic potential for pSS related dry eyes.