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

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Journal of Gastrointestinal Surgery Aims and scope

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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None of the authors has a conflict of interest to declare.

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Authors and Affiliations

  1. Division of Surgery, School of Graduate Entry Medicine and Health, University of Nottingham Medical School at Derby, Royal Derby Hospital, Uttoxeter Road, Derby, DE22 3DT, UK

    Imran Bhatti, Andrew Lee, Richard I. Hall, Jonathan N. Lund, Cristina Tufarelli & Michael Larvin

  2. School of Biomedical Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Victoria James

  3. Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, Nottingham University Hospitals, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Dileep N. Lobo

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  1. Imran Bhatti
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  2. Andrew Lee
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Correspondence to Imran Bhatti.

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Bhatti, I., Lee, A., James, V. et al. Knockdown of microRNA-21 Inhibits Proliferation and Increases Cell Death by Targeting Programmed Cell Death 4 (PDCD4) in Pancreatic Ductal Adenocarcinoma. J Gastrointest Surg 15, 199–208 (2011). https://doi.org/10.1007/s11605-010-1381-x

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