Circular RNA In Invasive and Recurrent Clinical Nonfunctioning Pituitary Adenomas: Expression Profiles and Bioinformatic Analysis.

BACKGROUND: The invasion and recurrence of clinical nonfunctioning pituitary adenomas (NFA) often lead to surgical treatment failure. Circular RNAs (circRNAs) are a novel class of RNAs whose 3' and 5' ends are joined together and have been shown to play important roles in cancer development. Until now, the roles of circRNAs have remained unclear in invasive and recurrent NFA.

METHODS: We detected and summarized the circRNA expression pattern in 75 NFA tissues from 10 noninvasive cases and 65 invasive cases and 9 pairs of NFA tumor tissues from 9 recurrent cases by circRNA microarrays. Accordingly, functional enrichment analysis and pathway analysis were performed and the circRNA-microRNA (miRNA) network was generated by bioinformatic analysis tools. Five new invasive NFA samples and 5 noninvasive NFA samples were collected to measure the microarray results.

RESULTS: A total of 570 dysregulated circRNAs (invasive tumor vs. noninvasive tumor) and 10 upregulated circRNAs (recurrent tumor tissue vs. first surgery tumor tissue) were identified based on the situation (fold change >2; P < 0.05). The parental genes of the dysregulated circRNAs in the comparison between invasion tumor and noninvasion tumor were found to be enriched in some cell adhesion signaling pathways such as Focal adhesion, Hippo signaling pathway, PI3K-Akt signaling pathway, and Adherens junction. The circRNA-miRNA network showed that the dysregulated circRNA may function as miRNA sponges.

CONCLUSIONS: This is the first study to conduct and comprehensively analyze the circRNA expression profile in invasive and recurrent NFA. Our finding will provide evidence for the significance of circRNAs in NFA diagnosis, prognosis, and clinical treatment.