Novel role of PELI3 as a potential biomarker for Sjogren's syndrome related dry eyes
Abstract
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. microRNAs (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 (PELI3), a negative regulator of inflammatory cytokines, as a predicted target. The mRNA microarray showed a decrease in PELI3 in pSS patients compared to healthy controls (p = 0.0731). Overexpression of miR-A mimic in HeLa cells resulted in decreased expression of PELI3, suggesting that it is a direct target for miR-A.
Conclusions
We have identified differentially expressed miRs and gene targets from CEC in pSS. PELI3, 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.
