Micro-RNA149 confers taxane resistance to malignant mesothelioma cells via regulation of P-glycoprotein expression

Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the de...

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Bibliographic Details
Published in:Cancer biology & therapy 2018-03, Vol.19 (3), p.181-187
Main Authors: Kenworthy, Rachael, Bosco, Dale B., DeLigio, James T., Zorio, Diego A. R.
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
ATP Binding Cassette Transporter, Subfamily B - genetics
ATP Binding Cassette Transporter, Subfamily B - metabolism
Cancer
Cell Line, Tumor
Drug Resistance, Multiple - genetics
Drug Resistance, Neoplasm - drug effects
Drug Resistance, Neoplasm - genetics
Gene Expression Regulation, Neoplastic - drug effects
Humans
Inhibitory Concentration 50
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Mesothelioma - drug therapy
Mesothelioma - genetics
Mesothelioma, Malignant
Micro-RNAs
MicroRNAs - metabolism
Multidrug Resistance
P-glycoprotein
Research Paper
Taxanes
Taxoids - pharmacology
Taxoids - therapeutic use
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Summary:Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the development of MDR is increased expression of multi-drug resistant protein 1 (MDR1), also known as P-glycoprotein (P-gp). P-gp is a membrane-associated efflux pump that can efficiently remove internalized taxane-base chemotherapeutics thus preventing drug accumulation and maintaining cellular viability. Consequently, investigation into the molecular mechanisms responsible for regulation of P-gp expression is necessary to facilitate treatment of MDR tumors. Using molecular and biochemical approaches, we identified that the micro-RNA, miRNA149, contributes to the development of MDR within malignant mesothelioma cells by regulating the expression of MDR1.
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2017.1415677