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Journal of Gastrointestinal Surgery
Published in: Journal of Gastrointestinal Surgery 1/2011

01-01-2011 | Original Article

Knockdown of microRNA-21 Inhibits Proliferation and Increases Cell Death by Targeting Programmed Cell Death 4 (PDCD4) in Pancreatic Ductal Adenocarcinoma

Authors: Imran Bhatti, Andrew Lee, Victoria James, Richard I. Hall, Jonathan N. Lund, Cristina Tufarelli, Dileep N. Lobo, Michael Larvin

Published in: Journal of Gastrointestinal Surgery | Issue 1/2011

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Abstract

Objective

This study aims to examine the expression of a panel of five microRNAs (miRNA) in pancreatic ductal adenocarcinoma (PDAC) and the functional effect of miR-21 inhibition in PDAC cell lines.

Background

miRNA are short, non-coding RNA molecules, which play important roles in several cellular processes by silencing expression of their target genes through translational repression or mRNA degradation. They are often aberrantly expressed in cancer, and this dysregulation can promote carcinogenesis by altering the expression of tumour suppressor or oncogenes.

Methods

miRNA expression levels were measured in 24 PDAC tumour/matched adjacent normal tissue samples and three PDAC cell lines using reverse transcription polymerase chain reaction. Levels of cell proliferation and death and expression of programmed cell death 4 (PDCD4; tumour suppressor) were studied in PDAC cells (MIA-Pa-Ca-2) in the absence or presence of a miR-21 inhibitor.

Results

PDAC primary tissues and cell lines displayed a consistent upregulation of miR-21 (P < 0.0001) and downregulation of both miR-148a (P < 0.0001) and miR-375 (P < 0.0001) relative to adjacent normal tissue. Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P < 0.0001). Inhibition of miR-21 in MIA-Pa-Ca-2 PDAC cells led to reduced cell proliferation (P < 0.01) and increased cell death (P < 0.01), with simultaneous increase in levels of the tumour suppressor, PDCD4 (P < 0.01).

Conclusion

miRNA expression profiles may be used as biomarkers for detecting pancreatic cancer. Moreover, miR-21 could be a predictor of disease progression and a possible therapeutic target in part by upregulating PDCD4 in pancreatic cancer.
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Metadata
Title
Knockdown of microRNA-21 Inhibits Proliferation and Increases Cell Death by Targeting Programmed Cell Death 4 (PDCD4) in Pancreatic Ductal Adenocarcinoma
Authors
Imran Bhatti
Andrew Lee
Victoria James
Richard I. Hall
Jonathan N. Lund
Cristina Tufarelli
Dileep N. Lobo
Michael Larvin
Publication date
01-01-2011
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 1/2011
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-010-1381-x

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