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Length variants of the ABCB1 3'-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. | LitMetric
Aim : To identify the exact length and possible length variations of the ABCB1 3'-UTR as important regulatory site for miRNA interaction of this drug transporter and its possible contribution to drug resistance.Materials & Methods : 3'-RACE and various standard PCR experiments were performed using cDNA of different human cell lines and liver tissue. The abundance of 3'-UTR fragments was analyzed using quantitative RT-PCR.Results : Five different ABCB1 3'-UTR length variants were identified. miRNA binding sites were located only on the three longer fragments. Imatinib-resistant leukemia cells expressed predominantly shorter 3'-UTRs, where miRNA binding sites are absent.Conclusion : Shortening of the ABCB1 3'-UTR causes loss of miRNA-dependent translational control leading to elevated ABCB1 protein levels.
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