Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice

Summary: miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size,...

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Autores principales:	Suheda Erener, Cara E. Ellis, Adam Ramzy, Maria M. Glavas, Shannon O’Dwyer, Sandra Pereira, Tom Wang, Janice Pang, Jennifer E. Bruin, Michael J. Riedel, Robert K. Baker, Travis D. Webber, Marina Lesina, Matthias Blüher, Hana Algül, Janel L. Kopp, Stephan Herzig, Timothy J. Kieffer
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	miR-216a β-cell mass diabetes pancreatic cancer PDAC biomarker Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/72b68c0d6c1547c3b0a24daccc37c95f
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spelling	oai:doaj.org-article:72b68c0d6c1547c3b0a24daccc37c95f2021-11-18T04:52:10ZDeletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice2666-379110.1016/j.xcrm.2021.100434https://doaj.org/article/72b68c0d6c1547c3b0a24daccc37c95f2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121002962https://doaj.org/toc/2666-3791Summary: miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line KrasG12D;Ptf1aCreER reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.Suheda ErenerCara E. EllisAdam RamzyMaria M. GlavasShannon O’DwyerSandra PereiraTom WangJanice PangJennifer E. BruinMichael J. RiedelRobert K. BakerTravis D. WebberMarina LesinaMatthias BlüherHana AlgülJanel L. KoppStephan HerzigTimothy J. KiefferElsevierarticlemiR-216aβ-cell massdiabetespancreatic cancerPDACbiomarkerMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100434- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	miR-216a β-cell mass diabetes pancreatic cancer PDAC biomarker Medicine (General) R5-920
spellingShingle	miR-216a β-cell mass diabetes pancreatic cancer PDAC biomarker Medicine (General) R5-920 Suheda Erener Cara E. Ellis Adam Ramzy Maria M. Glavas Shannon O’Dwyer Sandra Pereira Tom Wang Janice Pang Jennifer E. Bruin Michael J. Riedel Robert K. Baker Travis D. Webber Marina Lesina Matthias Blüher Hana Algül Janel L. Kopp Stephan Herzig Timothy J. Kieffer Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
description	Summary: miRNAs have crucial functions in many biological processes and are candidate biomarkers of disease. Here, we show that miR-216a is a conserved, pancreas-specific miRNA with important roles in pancreatic islet and acinar cells. Deletion of miR-216a in mice leads to a reduction in islet size, β-cell mass, and insulin levels. Single-cell RNA sequencing reveals a subpopulation of β-cells with upregulated acinar cell markers under a high-fat diet. miR-216a is induced by TGF-β signaling, and inhibition of miR-216a increases apoptosis and decreases cell proliferation in pancreatic cells. Deletion of miR-216a in the pancreatic cancer-prone mouse line KrasG12D;Ptf1aCreER reduces the propensity of pancreatic cancer precursor lesions. Notably, circulating miR-216a levels are elevated in both mice and humans with pancreatic cancer. Collectively, our study gives insights into how β-cell mass and acinar cell growth are modulated by a pancreas-specific miRNA and also suggests miR-216a as a potential biomarker for diagnosis of pancreatic diseases.
format	article
author	Suheda Erener Cara E. Ellis Adam Ramzy Maria M. Glavas Shannon O’Dwyer Sandra Pereira Tom Wang Janice Pang Jennifer E. Bruin Michael J. Riedel Robert K. Baker Travis D. Webber Marina Lesina Matthias Blüher Hana Algül Janel L. Kopp Stephan Herzig Timothy J. Kieffer
author_facet	Suheda Erener Cara E. Ellis Adam Ramzy Maria M. Glavas Shannon O’Dwyer Sandra Pereira Tom Wang Janice Pang Jennifer E. Bruin Michael J. Riedel Robert K. Baker Travis D. Webber Marina Lesina Matthias Blüher Hana Algül Janel L. Kopp Stephan Herzig Timothy J. Kieffer
author_sort	Suheda Erener
title	Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
title_short	Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
title_full	Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
title_fullStr	Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
title_full_unstemmed	Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
title_sort	deletion of pancreas-specific mir-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/72b68c0d6c1547c3b0a24daccc37c95f
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Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in mice

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