A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells

Oliver A. Kent, Michael Mullendore, Eric A. Wentzel, Pedro López-Romero, Aik Choon Tan, Hector Alvarez, Kristen West, Michael F. Ochs, Manuel Hidalgo, Dan E. Arking, Anirban Maitra, Joshua T. Mendell

Research output: Contribution to journalArticlepeer-review

107 Citations (Scopus)


MicroRNAs (miRNAs) are 21-24 nucleotide RNa molecules that regulate the translation and stability of target messenger RNAs. Abnormal miRNA expression is a common feature of diverse cancers. Several previous studies have classified miRNA expression in pancreatic ductal adenocarcinoma (pDaC), although no uniform pattern of miRNa dysregulation has emerged. To clarify these previous findings as well as to set the stage for detailed functional analyses, we performed global miRNA expression profiling of 21 human PDAC cell lines, the most extensive panel studied to date. Overall, 39 miRNAs were found to be dysregulated and have at least two-fold or greater differential expression in pDaC cell lines compared to control nontransformed pancreatic ductal cell lines. Several of these miRNAs show comparable dysregulation in first-passage patientderived xenografts. Initial functional analyses demonstrate that enforced expression of miRNas derived from the miR-200 family and the miR-17-92 cluster, both of which are overexpressed in pDaC cell lines, enhances proliferation. In contrast, inhibition of the miR-200 family, the miR-17-92 cluster, or miR-191 diminishes anchorage independent growth. Consistent with a known role for the miR-200 family in negatively regulating an epithelial-to-mesenchymal transition (eMT), the abundance of these miRNas correlated positively with e-cadherin expression and negatively with the eMT-associated transcription factor and established miR-200 target ZeB1. Finally, restituted expression of miR-34a, a miRNa whose expression is frequently lost in pDaC cell lines, abrogates growth, demonstrating that the anti-proliferative activity of this miRNa is operative in pDaC. These results, and the widespread availability of pDaC cell lines wherein the aforementioned data were generated, provide a valuable resource for the pancreatic cancer research community and will greatly facilitate functional studies essential for elucidating the consequences of miRNa dysregulation in pancreatic cancer.

Original languageEnglish
Pages (from-to)2013-2024
Number of pages12
JournalCancer Biology and Therapy
Issue number21
Publication statusPublished - 2009 Nov 1

Bibliographical note

Funding Information:
The authors wish to thank Michel Ouelette at the University of Nebraska for HPNE cells and Ming-Sound Tsao at the University of Toronto for HPDE cells. We also thank Alex Amiet and Devin Leake at Thermo Fisher Scientific (Dharmacon) for microRNA inhibitors, transfection reagents and consultation. This work was supported by grants from The Lustgarten Foundation for Pancreatic Cancer Research (to J.T.M.), The Sol Goldman Center for Pancreatic Cancer Research (to J.T.M), The Michael Rolfe Foundation for Pancreatic Cancer Research (to A.M), and the NIH (R01CA120185 to J.T.M., R01CA113669 and P50CA062924 to A.M., P01CA134292 to J.T.M. and A.M., and P30CA006973 to M.F.O.). J.T.M. is a Rita Allen Foundation Scholar and a Leukemia and Lymphoma Society Scholar. O.A.K. is a Life Sciences Research Foundation Fellow supported by Pfizer.


  • Gene expression
  • MiR-200
  • MicroRNA
  • Microarray
  • Oncogene
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


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