Abstract
Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. The present study identifies a series of miRNAs which were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues. Gemcitabine resistant MIA PaCa-2 cells possessed distinct ALDH-positive CSC fraction expressing stem cell markers OCT3/4 and CD44 and chemoresistance marker class IIIβ-tubulin (TUBB3) which decreases on transfection with miR-205 resulting in the restoration of chemosensitivity to gemcitabine.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Antineoplastic Agents / pharmacology*
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Cell Growth Processes / drug effects
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Cell Growth Processes / genetics
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Cell Line, Tumor
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Drug Resistance, Neoplasm
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Gemcitabine
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Gene Expression Profiling
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Humans
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MicroRNAs / biosynthesis
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MicroRNAs / genetics*
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Neoplasm Invasiveness
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / pathology
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Neoplastic Stem Cells / physiology*
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / genetics*
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Pancreatic Neoplasms / pathology
Substances
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Antineoplastic Agents
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MicroRNAs
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Deoxycytidine
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Gemcitabine