Title |
Dicer Regulates Differentiation and Viability during Mouse Pancreatic Cancer Initiation
|
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Published in |
PLOS ONE, May 2014
|
DOI | 10.1371/journal.pone.0095486 |
Pubmed ID | |
Authors |
John P. Morris, Renee Greer, Holger A. Russ, Guido von Figura, Grace E. Kim, Anke Busch, Jonghyeob Lee, Klemens J. Hertel, Seung Kim, Michael Mcmanus, Matthias Hebrok |
Abstract |
miRNA levels are altered in pancreatic ductal adenocarcinoma (PDA), the most common and lethal pancreatic malignancy, and intact miRNA processing is essential for lineage specification during pancreatic development. However, the role of miRNA processing in PDA has not been explored. Here we study the role of miRNA biogenesis in PDA development by deleting the miRNA processing enzyme Dicer in a PDA mouse model driven by oncogenic Kras. We find that loss of Dicer accelerates Kras driven acinar dedifferentiation and acinar to ductal metaplasia (ADM), a process that has been shown to precede and promote the specification of PDA precursors. However, unconstrained ADM also displays high levels of apoptosis. Dicer loss does not accelerate development of Kras driven PDA precursors or PDA, but surprisingly, we observe that mouse PDA can develop without Dicer, although at the expense of proliferative capacity. Our data suggest that intact miRNA processing is involved in both constraining pro-tumorigenic changes in pancreatic differentiation as well as maintaining viability during PDA initiation. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 3% |
Unknown | 34 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 23% |
Student > Ph. D. Student | 6 | 17% |
Student > Master | 5 | 14% |
Student > Doctoral Student | 4 | 11% |
Professor | 3 | 9% |
Other | 3 | 9% |
Unknown | 6 | 17% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 11 | 31% |
Medicine and Dentistry | 10 | 29% |
Biochemistry, Genetics and Molecular Biology | 5 | 14% |
Veterinary Science and Veterinary Medicine | 1 | 3% |
Unknown | 8 | 23% |