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A novel small nucleolar RNA‐derived microRNA‐1291 targets multidrug resistance‐associated protein 1 (MRP1/ABCC1)
Author(s) -
Pan Yuzhuo,
Yu Aiming
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1015.10
Subject(s) - abcc1 , microrna , biology , multiple drug resistance , multidrug resistance associated proteins , three prime untranslated region , transfection , messenger rna , untranslated region , drug resistance , microbiology and biotechnology , cancer research , atp binding cassette transporter , gene , transporter , genetics
Multidrug resistance‐associated protein (MRP1/ABCC1) is expressed ubiquitously in human tissues including the lung, testis, kidney, pancreas and placenta, and contributes to a variety of physiological functions including the extrusion of endobiotic and xenobiotic toxins. ABCC1 may also confer multidrug resistance (MDR) in cancer cells. As the posttranscriptional regulation of ABCC1 remains elusive, this study aimed to investigate the role of microRNAs in regulation of ABCC1 and the impact on cellular defense against xenobiotic drugs. Bioinformatics analysis showed that miRNA‐1291 might be derived from the small nucleolar RNA SNORA34, and target ABCC1 3′‐untranslated region (3′UTR). Using a novel splinted ligation RNA detection method, SNORA34 was found to be processed to miR‐1291 in PANC‐1 human pancreases cancer cells. Luciferase assay supported the action of miR‐1291 on ABCC1 3′UTR. ABCG2 mRNA and protein expression were dramatically down‐regulated in miR‐1291 stably‐transfected PANC‐1 cells with higher miR‐1291 expression. Intracellular drug accumulation and the sensitivity of cells to doxorubicin or mitoxantrone was significantly increased in PANC‐1 cells with higher miR‐1291 expression. These findings demonstrate the involvement of miR‐1291 in posttranscriptional regulation of ABCC1. Further studies on miRNA signaling may help develop novel strategy to overcome multidrug resistance.