An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells

Yusuke Yoshioka, Kaho Minoura, Ryou u. Takahashi, Fumitaka Takeshita, Toshiki Taya, Reiko Horii, Yayoi Fukuoka, Takashi Kato, Nobuyoshi Kosaka, Takahiro Ochiya

    Research output: Contribution to journalArticle

    70 Citations (Scopus)

    Abstract

    Background: Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance.Results: Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR.Conclusion: These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.

    Original languageEnglish
    Article number135
    JournalMolecular Cancer
    Volume10
    DOIs
    Publication statusPublished - 2011 Nov 3

    Fingerprint

    MicroRNAs
    Drug Resistance
    Breast Neoplasms
    Gene Expression
    Neoplasms
    Treatment Failure
    Pharmaceutical Preparations
    Down-Regulation
    Cell Proliferation
    Genome
    Apoptosis
    Cell Line
    Genes

    Keywords

    • Acgh
    • Breast cancer
    • Drug resistance
    • Gene expression
    • Microrna

    ASJC Scopus subject areas

    • Cancer Research
    • Molecular Medicine
    • Oncology

    Cite this

    An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells. / Yoshioka, Yusuke; Minoura, Kaho; Takahashi, Ryou u.; Takeshita, Fumitaka; Taya, Toshiki; Horii, Reiko; Fukuoka, Yayoi; Kato, Takashi; Kosaka, Nobuyoshi; Ochiya, Takahiro.

    In: Molecular Cancer, Vol. 10, 135, 03.11.2011.

    Research output: Contribution to journalArticle

    Yoshioka, Yusuke ; Minoura, Kaho ; Takahashi, Ryou u. ; Takeshita, Fumitaka ; Taya, Toshiki ; Horii, Reiko ; Fukuoka, Yayoi ; Kato, Takashi ; Kosaka, Nobuyoshi ; Ochiya, Takahiro. / An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells. In: Molecular Cancer. 2011 ; Vol. 10.
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