Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue

Abstract Background Only a limited number of biomarkers guide personalized management of pancreatic neuroendocrine tumors (PanNETs). Transcriptome profiling of microRNA (miRs) and mRNA has shown value in segregating PanNETs and identifying patients more likely to respond to treatment. Because miRs a...

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Main Authors: N Matyasovska, N Valkova, M Gala, S Bendikova, A Abdulhamed, V. Palicka, Neil Renwick, Pavol Čekan, Evan Paul
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14043-w
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author N Matyasovska
N Valkova
M Gala
S Bendikova
A Abdulhamed
V. Palicka
Neil Renwick
Pavol Čekan
Evan Paul
author_facet N Matyasovska
N Valkova
M Gala
S Bendikova
A Abdulhamed
V. Palicka
Neil Renwick
Pavol Čekan
Evan Paul
author_sort N Matyasovska
collection DOAJ
description Abstract Background Only a limited number of biomarkers guide personalized management of pancreatic neuroendocrine tumors (PanNETs). Transcriptome profiling of microRNA (miRs) and mRNA has shown value in segregating PanNETs and identifying patients more likely to respond to treatment. Because miRs are key regulators of mRNA expression, we sought to integrate expression data from both RNA species into miR-mRNA interaction networks to advance our understanding of PanNET biology. Methods We used deep miR/mRNA sequencing on six low-grade/high-risk, well-differentiated PanNETs compared with seven non-diseased tissues to identify differentially expressed miRs/mRNAs. Then we crossed a list of differentially expressed mRNAs with a list of in silico predicted mRNA targets of the most and least abundant miRs to generate high probability miR-mRNA interaction networks. Results Gene ontology and pathway analyses revealed several miR-mRNA pairs implicated in cellular processes and pathways suggesting perturbed neuroendocrine function (miR-7 and Reg family genes), cell adhesion (miR-216 family and NLGN1, NCAM1, and CNTN1; miR-670 and the claudins, CLDN1 and CLDN2), and metabolic processes (miR-670 and BCAT1/MPST; miR-129 and CTH). Conclusion These novel miR-mRNA interaction networks identified dysregulated pathways not observed when assessing mRNA alone and provide a foundation for further investigation of their utility as diagnostic and predictive biomarkers.
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spelling doaj-art-b1d2c191027b42fd812d3c80e631d69f2025-08-20T02:17:09ZengBMCBMC Cancer1471-24072025-04-0125111310.1186/s12885-025-14043-wDeep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissueN Matyasovska0N Valkova1M Gala2S Bendikova3A Abdulhamed4V. Palicka5Neil Renwick6Pavol Čekan7Evan Paul8MultiplexDX, s.r.o, Comenius University Science ParkMultiplexDX, s.r.o, Comenius University Science ParkMultiplexDX, s.r.o, Comenius University Science ParkMultiplexDX, s.r.o, Comenius University Science ParkLaboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen’s UniversityInstitute of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove, University Hospital, Charles UniversityLaboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen’s UniversityMultiplexDX, s.r.o, Comenius University Science ParkMultiplexDX, s.r.o, Comenius University Science ParkAbstract Background Only a limited number of biomarkers guide personalized management of pancreatic neuroendocrine tumors (PanNETs). Transcriptome profiling of microRNA (miRs) and mRNA has shown value in segregating PanNETs and identifying patients more likely to respond to treatment. Because miRs are key regulators of mRNA expression, we sought to integrate expression data from both RNA species into miR-mRNA interaction networks to advance our understanding of PanNET biology. Methods We used deep miR/mRNA sequencing on six low-grade/high-risk, well-differentiated PanNETs compared with seven non-diseased tissues to identify differentially expressed miRs/mRNAs. Then we crossed a list of differentially expressed mRNAs with a list of in silico predicted mRNA targets of the most and least abundant miRs to generate high probability miR-mRNA interaction networks. Results Gene ontology and pathway analyses revealed several miR-mRNA pairs implicated in cellular processes and pathways suggesting perturbed neuroendocrine function (miR-7 and Reg family genes), cell adhesion (miR-216 family and NLGN1, NCAM1, and CNTN1; miR-670 and the claudins, CLDN1 and CLDN2), and metabolic processes (miR-670 and BCAT1/MPST; miR-129 and CTH). Conclusion These novel miR-mRNA interaction networks identified dysregulated pathways not observed when assessing mRNA alone and provide a foundation for further investigation of their utility as diagnostic and predictive biomarkers.https://doi.org/10.1186/s12885-025-14043-wPancreatic neuroendocrine tumorsMicroRNAmRNABiomarkersmiR-mRNA interaction networks
spellingShingle N Matyasovska
N Valkova
M Gala
S Bendikova
A Abdulhamed
V. Palicka
Neil Renwick
Pavol Čekan
Evan Paul
Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
BMC Cancer
Pancreatic neuroendocrine tumors
MicroRNA
mRNA
Biomarkers
miR-mRNA interaction networks
title Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
title_full Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
title_fullStr Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
title_full_unstemmed Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
title_short Deep sequencing reveals distinct microRNA-mRNA signatures that differentiate pancreatic neuroendocrine tumor from non-diseased pancreas tissue
title_sort deep sequencing reveals distinct microrna mrna signatures that differentiate pancreatic neuroendocrine tumor from non diseased pancreas tissue
topic Pancreatic neuroendocrine tumors
MicroRNA
mRNA
Biomarkers
miR-mRNA interaction networks
url https://doi.org/10.1186/s12885-025-14043-w
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