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

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80 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

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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    Yoshioka, Y., Minoura, K., Takahashi, R. U., Takeshita, F., Taya, T., Horii, R., Fukuoka, Y., Kato, T., Kosaka, N., & Ochiya, T. (2011). An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells. Molecular Cancer, 10, [135]. https://doi.org/10.1186/1476-4598-10-135