掷骰子
克拉斯
小RNA
生物
胰腺癌
癌症研究
胰腺
细胞生物学
腺泡细胞
癌症
内分泌学
RNA干扰
遗传学
基因
核糖核酸
结直肠癌
作者
John P. Morris,Renee Greer,Holger A. Russ,Guido von Figura,Grace Kim,Anke Busch,Jonghyeob Lee,Klemens J. Hertel,Seung Kim,Michael T. McManus,Matthias Hebrok
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2014-05-01
卷期号:9 (5): e95486-e95486
被引量:27
标识
DOI:10.1371/journal.pone.0095486
摘要
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.
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