miRNA-mediated regulation of Mucin-type O-Glycosylation pathway: a putative mechanism of salivary gland dysfunction in Sjögren's syndrome

Objectives: To investigate microRNA (miRNA)-potentially implicated in primary Sjögren’s syndrome (pSS)-related salivary hypofunction in labial salivary glands and to explore miRNA-mediated mechanisms underlying oral dryness and altered rheology focusing on mucin O-glycosylation pathway. Methods: We performed miRNA expression profiling in minor salivary gland samples of pSS patients presenting a different impairment in their unstimulated salivary flow rate (USFR). A computational in silico analysis was performed to identify genes and pathways that might be modulated by the deregulated miRNAs that we had identified. To confirm in silico analysis, expression levels of genes encoding for glycosyltransferases and glycan-processing enzymes were investigated by using Human Glycosylation- RT² Profiler™ PCR Array. Results: Among 754 miRNA analyzed, we identified 126 miRNAs that were significantly de-regulated in pSS compared to controls, with a trend that was inversely proportional with the impairment of salivary flow rates. An in silico approach pinpointed that several upregulated miRNAs in pSS patients target important genes in the mucin O-glycosylation. We confirmed this prediction by qRT-PCR, highlighting the downregulation of some glycosyltransferase and glycosidase genes in pSS samples compared to controls, such as GALNT1, responsible for mucin-7 glycosylation. Conclusion: Collectively, our data suggest that the expression of different predicted miRNA-target genes in the mucin type O-glycan biosynthesis pathway is altered in pSS patients with low salivary flow and that miRNome could influence the glycosidases expression levels and consequently the rheology in pSS.