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,...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121002962 |
| _version_ | 1818402018973188096 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T08:01:42Z |
| format | Article |
| id | doaj.art-72b68c0d6c1547c3b0a24daccc37c95f |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-12-14T08:01:42Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-72b68c0d6c1547c3b0a24daccc37c95f2022-12-21T23:10:21ZengElsevierCell Reports Medicine2666-37912021-11-01211100434Deletion of pancreas-specific miR-216a reduces beta-cell mass and inhibits pancreatic cancer progression in miceSuheda Erener0Cara E. Ellis1Adam Ramzy2Maria M. Glavas3Shannon O’Dwyer4Sandra Pereira5Tom Wang6Janice Pang7Jennifer E. Bruin8Michael J. Riedel9Robert K. Baker10Travis D. Webber11Marina Lesina12Matthias Blüher13Hana Algül14Janel L. Kopp15Stephan Herzig16Timothy J. Kieffer17Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, GermanyDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, ON, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaComprehensive Cancer Center Munich, Technical University of Munich, Munich, GermanyHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany; Medical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, GermanyComprehensive Cancer Center Munich, Technical University of Munich, Munich, GermanyDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, CanadaInstitute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany; Technical University Munich, 85764 Neuherberg, Germany; Deutsches Zentrum für Diabetesforschung, 85764 Neuherberg, GermanyDepartment of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada; Department of Surgery, University of British Columbia, Vancouver, BC, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379121002962miR-216aβ-cell massdiabetespancreatic cancerPDACbiomarker |
| spellingShingle | 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 Cell Reports Medicine miR-216a β-cell mass diabetes pancreatic cancer PDAC biomarker |
| title | 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_short | 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 |
| topic | miR-216a β-cell mass diabetes pancreatic cancer PDAC biomarker |
| url | http://www.sciencedirect.com/science/article/pii/S2666379121002962 |
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