Length variants of the ABCB1 3′-UTR and loss of miRNA binding sites: possible consequences in regulation and pharmacotherapy resistance. (March 2016)

• Record Type: Journal Article
• Authors: Bruhn, Oliver; Drerup, Katharina; Kaehler, Meike; Haenisch, Sierk; Röder, Christian; Cascorbi, Ingolf
• Is Part Of: Pharmacogenomics. Volume 17:Number 4(2016)
• Page Start: 327
• Page End: 340
• Publication Date: 2016-03
• Subjects: drug resistance -- MDR1 -- miRNA -- P-glycoprotein -- polyadenylation -- post-transcriptional regulation; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.15.175
• Languages: English
• ISSNs: 1462-2416

Abstract

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.