Loss of cellular homeostasis in Sjogren syndrome is associated with miRNA dysregulation and IFN-g-mediated overexpression of ATF6a and SEL1L

Secretory dysfunction of salivary glands (SG) from Sjogren syndrome (SS)-patients has been associated with altered homeostasis, upregulation of the ATF6a transcription factor, which participates in the UPR and ERAD components, such as SEL1L. In three dimensional (3D)-acini, ATF6a and SEL1L mRNA levels increased in response to IFN-g, but the mechanism involved is unknown. Here, we characterized the global profile of small RNAs (sRNAs) in SG from SS-patients and controls with functional emphasis on hsa-miR-424-5p, which is predicted to target ATF6a and SEL1L mRNAs.sRNA next generation sequencing (NGS) was employed to identify miRNAs differentially expressed between SG from SS-patients and controls. Taqman assays validated hsa-miR-424-5p levels in SG from 16 SS-patients and 8 controls and these values were correlated with ATF6a and SEL1L mRNA levels. Functional assays involved IFN-g stimulation 3D-acini and chemically-synthesized hsa-miR-424-5p mimics and inhibitors.