Genome wide analysis of circulating miRNAs in growth hormone secreting pituitary neuroendocrine tumor patients’ plasma

Abstract

Funding Information: The financial support given by NSFC with Grant No. 11874034, Taishan Scholar Program of Shandong No. ts201712054, and Shandong Science and Technology Enterprise Innovation Capacity Enhancement Project (2021TSGC1036) are highly appreciated for this research. Publisher Copyright: Copyright © 2022 Niedra, Peculis, Litvina, Megnis, Madrika, Balcere, Romanovs, Steina, Stukens, Breiksa, Nazarovs, Sokolovska, Liutkeviciene, Vilkevicute, Konrade and Rovite.Background: Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs versus assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs versus other PitNET types and healthy individuals. Design: We compared plasma miRNA content and levels before and after surgery focusing on GH secreting PitNET patients. Selected miRNA candidates from our data and literature were then tested in a longitudinal manner in somatostatin analogues (SSA) treatment group. Additionally, we validated selected targets in an independent GH secreting PitNET group. Methods: miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results: Whole miRNA sequencing discovered a total of 16 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients’ plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. mir-625-5p was found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. miR-625-5p alongside miR-130b-3p were also found to be downregulated in GH PitNETs compared to healthy individuals. Conclusions: Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p can distinguish GH secreting PitNETs from other PitNET types and healthy controls warranting further research on these miRNAs for treatment efficacy.publishersversionPeer reviewe