Biological Functions of Circulating miRNAs in Patients with Chronic Pancreatitis Undergoing Total Pancreatectomy with Islet Autotransplantation
1Baylor University Medical Ctr, Dallas, TX, 2Baylor University, Waco, TX, 3-Baylor University Medical Center, Dallas, TX, 4Baylor University Medical Center, Dallas, TX
Meeting: 2022 American Transplant Congress
Abstract number: 1179
Keywords: Graft function, Islets, Monitoring, Pancreatitis
Topic: Clinical Science » Pancreas » 65 - Pancreas and Islet: All Topics
Session Information
Session Name: Pancreas and Islet: All Topics
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Our previous reports showed that in patients with Chronic Pancreatitis (CP), specific microRNAs (miRNA) were elevated in circulation before, during islet infusion and after TPIAT. We selected a panel of 12 miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-320d, hsa-miR-122-5p, hsa-miR-200c-3p, hsa-let-7e-5p, hsa-miR-125b-5p, hsa-miR-99b-5p) to assess whether these miRNAs exert important biological functions in pancreas in the context of CP.
*Methods: Over-Representation Analysis (ORA), mRNA targets in pancreas and their networks were assessed using (experimentally validated) miRNet, a miRNA-centric network visual analytics platform and miRNA Enrichment and Annotation tool (miEAA, Version 2.0).
*Results: Selected circulating miRNAs are enriched in pancreas but also expressed in other tissues. A subset of these miRNAs was enriched in other diseases including cancer and fibrosis. Notably, hsa-miR-125b-5p, hsa-miR-216a-5p, hsa-miR-221-3p and hsa-miR-29b-3p were enriched in fibrosis. These miRNAs target approximately 2888 mRNAs in pancreas, with overlapping networks and demonstrate interactions with 76 small molecules. Interestingly, hsa-miR-99b-5p, hsa-miR-125b-5p and hsa-miR-221-3p exhibit interactions with morphine; hsa-miR-148a-3p, hsa-miR-29b-3p, hsa-miR-200c-3p, hsa-miR-375 and hsa-miR-122-5p exhibit interactions with glucose. Further, we analyzed common mRNA targets between this panel of miRNAs and genes mapped based on variants associated with pancreatitis (identified in Genome Wide Association Studies (GWAS)) (Figure 1). Of the 187 variants with 112 mapped genes associated with pancreatitis, we identified 39 genes as targets of specific miRNAs (Figure 1). Of these, PLXNA1, MBOAT2, NANOS1, DDI2, PPP1R16B, KCNJ3, KLF7, JAZF1, ADAMTS18, NPAS3 and DNAJC16 interacted with 2 or more miRNAs.
*Conclusions: miRNAs elevated during TPIAT may exert specific biological functions in the pancreas during CP pathogenesis and their elevation in circulation may indicate specific cellular events during pancreatic inflammation and fibrosis, warranting further investigations.
To cite this abstract in AMA style:
Vasu S, Darden C, Liu Y, Lawrence M, Naziruddin B. Biological Functions of Circulating miRNAs in Patients with Chronic Pancreatitis Undergoing Total Pancreatectomy with Islet Autotransplantation [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/biological-functions-of-circulating-mirnas-in-patients-with-chronic-pancreatitis-undergoing-total-pancreatectomy-with-islet-autotransplantation/. Accessed March 26, 2023.« Back to 2022 American Transplant Congress