Circulating Y-RNAs, a predicted function controlling the Immune System, Cell Signaling, and DNA Replication in Pediatric Patients with Pilocytic and Diffuse Astrocytoma

Abstract

Background. Y-RNAs are small noncoding RNAs firstly identified in patients suffering the Sjögren’s syndrome and lupus erythematosus, having different predicted cellular functions. In this work, circulating Y-RNAs were detected in blood serum from pediatric patients with pilocytic or diffuse astrocytoma, by means of the HTA 2.0 arrays. In addition, a bioinformatic approximation of the possible biological functions of Y-RNAs was determined with the “Random Forest” and “Vector Support Machine” algorithms. Results. Data showed a differential expression of RNY-3, RNY-4, and -5 in tumors relative to the control. Meanwhile, RNY-1 was shown to be highly upregulated in the Diffuse condition versus the Pilocytic one. The bioinformatic analysis showed the interaction of all these Y-RNAs with different proteins, but RNY-4 and RNY-5 had the highest scores of interaction with the Claudin domain-containing protein 1, isoform α and Toll-like receptor 5, and the Hyaluronidase-1 isoform 3. Because Y-RNAs are processed in vivo to produce fragments through RNase processing, a second analysis was performed to determine the Y-RNAs loop domain interactions with these receptors. Results showed the highest score of interaction for RNY-3/B cell receptor CD22 isoform 1, followed by RNY-4/Toll-like receptor 7 and 3. Conclusions. Altogether, our results showed, for the first time a differential expression of circulating Y-RNAs in pediatric astrocytoma, allowing to distinguish pediatric patients without cancer from patients with pediatric diffuse or pilocytic astrocytoma and their potential involvement in regulating diverse biological processes, such as immune activation or suppression, cell signaling, selective transcription, and cell proliferation through DNA replication activation.