Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells

Hua Zhu, Hao Wu, Xiuping Liu, Brad R. Evans, Daniel J. Medina, Chang Gong Liu, Jin-Ming Yang

Research output: Contribution to journalArticle

358 Citations (Scopus)

Abstract

MicroRNAs are short non-coding RNA molecules able to affect stability and/or translation of mRNA, thereby regulating the expression of genes involved in many biological processes. We report here that microRNAs miR-27a and miR-451 are involved in activating the expression of P-glycoprotein, the MDR1 gene product that confers cancer cell resistance to a broad range of chemotherapeutics. We showed that expressions of miR-27a and miR-451 were up-regulated in multidrug resistant (MDR) cancer cell lines A2780DX5 and KB-V1, as compared with their parental lines A2780 and KB-3-1. Treatment of A2780DX5 cells with the antagomirs of miR-27a or miR-451 decreased the expression of P-glycoprotein and MDR1 mRNA. In contrast, the mimics of miR-27a and miR-451 increased MDR1 expression in the parental cells A2780. The sensitivity to and intracellular accumulation of cytotoxic drugs that are transported by P-glycoprotein were enhanced by the treatment with the antagomirs of miR-27a or miR-451. Our results demonstrate for the first time the roles of microRNAs in the regulation of drug resistance mediated by MDR1/P-glycoprotein, and suggest the potential for targeting miR-27a and miR-451 as a therapeutic strategy for modulating MDR in cancer cells.

Original languageEnglish (US)
Pages (from-to)582-588
Number of pages7
JournalBiochemical Pharmacology
Volume76
Issue number5
DOIs
StatePublished - Sep 1 2008

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P-Glycoprotein
MicroRNAs
Cells
Neoplasms
Genes
Biological Phenomena
Untranslated RNA
Messenger RNA
Protein Biosynthesis
Drug Resistance
Pharmaceutical Preparations
Gene Expression
Cell Line
Molecules
Antagomirs
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Zhu, Hua ; Wu, Hao ; Liu, Xiuping ; Evans, Brad R. ; Medina, Daniel J. ; Liu, Chang Gong ; Yang, Jin-Ming. / Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. In: Biochemical Pharmacology. 2008 ; Vol. 76, No. 5. pp. 582-588.
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Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. / Zhu, Hua; Wu, Hao; Liu, Xiuping; Evans, Brad R.; Medina, Daniel J.; Liu, Chang Gong; Yang, Jin-Ming.

In: Biochemical Pharmacology, Vol. 76, No. 5, 01.09.2008, p. 582-588.

Research output: Contribution to journalArticle

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