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Regulation of breast cancer resistance protein (BCRP/ABCG2) by microRNA‐328
Author(s) -
Pan Yuzhuo,
Morris Marilyn,
Yu Aiming
Publication year - 2010
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.24.1_supplement.964.14
Subject(s) - abcg2 , antagomir , microrna , transfection , luciferase , cancer research , mitoxantrone , chemistry , untranslated region , biology , pharmacology , messenger rna , transporter , atp binding cassette transporter , gene , biochemistry , chemotherapy , genetics
Breast cancer resistance protein (BCRP/ABCG2) is a membrane transporter that affects pharmacokinetic properties of many anticancer drugs. However, ABCG2 post‐transcriptional regulation and role of microRNAs (miRNAs) in drug disposition remain elusive. Computational analyses indicated that microRNA‐328 (miR‐328) might readily target the 3′‐untranslated region (3′UTR) of ABCG2. We then noted that 1) the levels of miR‐328 and ABCG2 in MCF‐7 and MCF‐7/MX100 breast cancer cells were inversely related, and 2) the levels of miR‐328 could be rescued in MCF‐7/MX100 cells after transfection with a miR‐328‐expressing plasmid. Luciferase assays showed that ABCG2 3′‐UTR‐luciferase activity was decreased more than 50% in MCF‐7/MX100 cells after transfection with miR‐328‐expressing plasmid, the activity was increased over 100% in MCF‐7 cells by a miR‐328 antagomir. Furthermore, ABCG2 protein expression was down‐regulated when miR‐328 was over‐expressed, and ABCG2 protein expression was up‐regulated when miR‐328 was inhibited by selective antagomir, which altered intracellular mitoxantrone accumulation and cell sensitivity to mitoxantrone, Together, these findings suggest that miR‐328 targets ABCG2 3′UTR, controls ABCG2 protein expression, and affects drug disposition. This project was supported by UB Interdisciplinary Research Development Fund, and in part by NIH R01DA021172.