Dicer is required for maintenance of adult pancreatic acinar cell identity and plays a role in Kras-driven pancreatic neoplasia

Yue J. Wang, Florencia McAllister, Jennifer M. Bailey, Sherri Gae Scott, Audrey M. Hendley, Steven D. Leach, Bidyut Ghosh

Research output: Contribution to journalArticle

Abstract

The role of miRNA processing in the maintenance of adult pancreatic acinar cell identity and during the initiation and progression of pancreatic neoplasia has not been studied in detail. In this work, we deleted Dicer specifically in adult pancreatic acinar cells, with or without simultaneous activation of oncogenic Kras. We found that Dicer is essential for the maintenance of acinar cell identity. Acinar cells lacking Dicer showed increased plasticity, as evidenced by loss of polarity, initiation of epithelial-to-mesenchymal transition (EMT) and acinar-to-ductal metaplasia (ADM). In the context of oncogenic Kras activation, the initiation of ADM and pancreatic intraepithelial neoplasia (PanIN) were both highly sensitive to Dicer gene dosage. Homozygous Dicer deletion accelerated the formation of ADM but not PanIN. In contrast, heterozygous Dicer deletion accelerated PanIN initiation, revealing complex roles for Dicer in the regulation of both normal and neoplastic pancreatic epithelial identity.

Original languageEnglish (US)
Article number0113127
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 18 2014

Fingerprint

acinar cells
Acinar Cells
metaplasia
Metaplasia
Chemical activation
Maintenance
neoplasms
MicroRNAs
Plasticity
Neoplasms
Genes
gene dosage
Epithelial-Mesenchymal Transition
Gene Dosage
Processing
microRNA

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wang, Y. J., McAllister, F., Bailey, J. M., Scott, S. G., Hendley, A. M., Leach, S. D., & Ghosh, B. (2014). Dicer is required for maintenance of adult pancreatic acinar cell identity and plays a role in Kras-driven pancreatic neoplasia. PLoS One, 9(11), [0113127]. https://doi.org/10.1371/journal.pone.0113127

Dicer is required for maintenance of adult pancreatic acinar cell identity and plays a role in Kras-driven pancreatic neoplasia. / Wang, Yue J.; McAllister, Florencia; Bailey, Jennifer M.; Scott, Sherri Gae; Hendley, Audrey M.; Leach, Steven D.; Ghosh, Bidyut.

In: PLoS One, Vol. 9, No. 11, 0113127, 18.11.2014.

Research output: Contribution to journalArticle

Wang, Yue J. ; McAllister, Florencia ; Bailey, Jennifer M. ; Scott, Sherri Gae ; Hendley, Audrey M. ; Leach, Steven D. ; Ghosh, Bidyut. / Dicer is required for maintenance of adult pancreatic acinar cell identity and plays a role in Kras-driven pancreatic neoplasia. In: PLoS One. 2014 ; Vol. 9, No. 11.
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