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.

Gender Predilection in Sporadic Parathyroid Adenomas

“…We have previously shown a differential circRNA profile at the tissue level between sporadic parathyroid adenomas and normal parathyroid tissue, suggesting the role of epigenetic changes in the pathogenesis of these tumors [55]. Moreover, we demonstrated a differential expression profile of circRNAs between male and female patients.…”

“…Although several studies have identified differential miRNA profiling between normal parathyroid glands and parathyroid tumors, as well as among different types of parathyroid tumors (adenoma vs. carcinoma vs. atypical adenoma) [62,63], the role of miRNAs in mediating gender biases in parathyroid adenoma-induced pHPT is as yet understudied and remains to be elucidated. In our study [55], we also identified several miRNAs that are linked to the profile of differentially expressed circRNAs in male patients compared to female patients with sporadic parathyroid adenomas. Among them, miRNA-1184 was the most frequently reported [55].…”

“…In our study [55], we also identified several miRNAs that are linked to the profile of differentially expressed circRNAs in male patients compared to female patients with sporadic parathyroid adenomas. Among them, miRNA-1184 was the most frequently reported [55]. The tissue expression of miRNA-1184 has been identified as a key regulator in the progression of prostate cancer by targeting specific transcription factors [64], while it was also found to play a significant role in differentiating high-risk women who develop breast cancer from those who remain cancer-free [65], suggesting that it may be differentially affected by sex hormones.…”

“…As a result of this closed structure, circRNAs have been shown to be highly stable and largely resistant to RNA degradation pathways [57], which suggests that circRNAs may be more useful molecular biomarkers for human diseases than linear non-coding RNAs. In our study, we identified 19 circRNAs that were significantly up-regulated and four circRNAs that were significantly down-regulated in parathyroid tumors from male patients compared to females [55], but whether these differences may contribute to differences between genders in sporadic parathyroid adenomas remains unknown.…”

Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application

“…Cancer. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), short micro-RNAs (miRNAs), and circular RNAs (circRNAs), control various levels of gene expression in disease, such as epigenetic memory, transcription, RNA splicing, editing, translation, and possibly tumorigenesis [63,64]. Recent evidence has suggested that a number of ncRNAs play crucial roles in the development of lung cancer.…”