A Role for Circular Non-Coding RNAs in the Pathogenesis of Sporadic Parathyroid Adenomas and the Impact of Gender-Specific Epigenetic Regulation

Abstract

Epigenetic changes, including altered small non-coding RNAs, appear to be implicated in the pathogenesis of sporadic parathyroid adenomas (PAs). In this study, we investigated the circular RNAs (circRNAs) expression profile in sporadic PAs. Sixteen tissue samples of sporadic PAs, and four samples of normal parathyroid tissue (NPT) were investigated. Sample preparation and microarray hybridization were performed based on the Arraystar’s standard protocols, and circRNAs sequences were predicted by bioinformatics tools. We identified 35 circRNAs that were differentially expressed in sporadic PAs compared to NPT; 22 were upregulated, and 13 were downregulated, according to the pre-defined thresholds of fold-change > 2.0 and p < 0.05. In the subgroup analysis of PAs from male patients (n = 7) compared to PAs from female patients (n = 9), we also find a different expression profile. In particular, 19 circRNAs were significantly upregulated, and four circRNAs were significantly downregulated in male patients, compared to female counterparts. We show here for the first time a differential circRNA expression pattern in sporadic PAs compared to NPT, and a different expression profile in PA samples from male compared to female patients, suggesting an epigenetic role in the PA pathogenesis, and also an effect of gender in the epigenetic regulation of PAs.

Keywords

• parathyroid adenomas
• pathogenesis
• epigenetics
• non-coding RNAs
• circular RNAs