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 Arking, Anirban Maitra, Joshua T. Mendell

Research output: Contribution to journalArticle

Abstract

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 (US)
Pages (from-to)2013-2024
Number of pages12
JournalCancer Biology and Therapy
Volume8
Issue number21
StatePublished - Nov 1 2009

Fingerprint

MicroRNAs
Adenocarcinoma
Cell Line
Epithelial-Mesenchymal Transition
Pancreatic Neoplasms
Cadherins
Growth
Heterografts
Transcription Factors
Nucleotides
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

Kent, O. A., Mullendore, M., Wentzel, E. A., López-Romero, P., Tan, A. C., Alvarez, H., ... Mendell, J. T. (2009). A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biology and Therapy, 8(21), 2013-2024.

A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. / Kent, Oliver A.; Mullendore, Michael; Wentzel, Eric A.; López-Romero, Pedro; Tan, Aik Choon; Alvarez, Hector; West, Kristen; Ochs, Michael F.; Hidalgo, Manuel; Arking, Dan; Maitra, Anirban; Mendell, Joshua T.

In: Cancer Biology and Therapy, Vol. 8, No. 21, 01.11.2009, p. 2013-2024.

Research output: Contribution to journalArticle

Kent, OA, Mullendore, M, Wentzel, EA, López-Romero, P, Tan, AC, Alvarez, H, West, K, Ochs, MF, Hidalgo, M, Arking, D, Maitra, A & Mendell, JT 2009, 'A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells', Cancer Biology and Therapy, vol. 8, no. 21, pp. 2013-2024.
Kent OA, Mullendore M, Wentzel EA, López-Romero P, Tan AC, Alvarez H et al. A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. Cancer Biology and Therapy. 2009 Nov 1;8(21):2013-2024.
Kent, Oliver A. ; Mullendore, Michael ; Wentzel, Eric A. ; López-Romero, Pedro ; Tan, Aik Choon ; Alvarez, Hector ; West, Kristen ; Ochs, Michael F. ; Hidalgo, Manuel ; Arking, Dan ; Maitra, Anirban ; Mendell, Joshua T. / A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells. In: Cancer Biology and Therapy. 2009 ; Vol. 8, No. 21. pp. 2013-2024.
@article{5c1543ab1ca3431e87801492fa24cb4a,
title = "A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells",
abstract = "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.",
keywords = "Gene expression, Microarray, MicroRNA, MiR-200, Oncogene, Pancreatic ductal adenocarcinoma",
author = "Kent, {Oliver A.} and Michael Mullendore and Wentzel, {Eric A.} and Pedro L{\'o}pez-Romero and Tan, {Aik Choon} and Hector Alvarez and Kristen West and Ochs, {Michael F.} and Manuel Hidalgo and Dan Arking and Anirban Maitra and Mendell, {Joshua T.}",
year = "2009",
month = "11",
day = "1",
language = "English (US)",
volume = "8",
pages = "2013--2024",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "21",

}

TY - JOUR

T1 - A resource for analysis of microRNA expression and function in pancreatic ductal adenocarcinoma cells

AU - Kent, Oliver A.

AU - Mullendore, Michael

AU - Wentzel, Eric A.

AU - López-Romero, Pedro

AU - Tan, Aik Choon

AU - Alvarez, Hector

AU - West, Kristen

AU - Ochs, Michael F.

AU - Hidalgo, Manuel

AU - Arking, Dan

AU - Maitra, Anirban

AU - Mendell, Joshua T.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - 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.

AB - 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.

KW - Gene expression

KW - Microarray

KW - MicroRNA

KW - MiR-200

KW - Oncogene

KW - Pancreatic ductal adenocarcinoma

UR - http://www.scopus.com/inward/record.url?scp=73549106305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73549106305&partnerID=8YFLogxK

M3 - Article

C2 - 20037478

AN - SCOPUS:73549106305

VL - 8

SP - 2013

EP - 2024

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 21

ER -