Title page for etd-0624113-191725


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URN etd-0624113-191725
Author Chi-Hsiang Chiang
Author's Email Address No Public.
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Department Institute of Biomedical Sciences
Year 2012
Semester 2
Degree Ph.D.
Type of Document
Language English
Title Regulation of microRNA-182 and its functional role in breast cancer
Date of Defense 2013-07-12
Page Count 103
Keyword
  • RECK
  • β-catenin
  • microRNA
  • matrix metalloproteinase
  • Abstract MicroRNAs (MiRNAs) are endogenous small non-coding RNAs which negatively regulate gene expression by inducing translation repression or mRNA cleavage. MiR-182 is a member of the miR-183 cluster which is located at human chromosome 7q32 region and is over-expressed in several types of human cancer. Recent studies demonstrated that miR-182 functions as an oncogenic miRNA via inhibition of several tumor suppressor genes like FOXO3, FOXO1, BRCA1 and MTSS1. In the first part of this study, we demonstrated that miR-182 is over-expressed in human breast tumor tissues and cell lines. In addition, we found that β-catenin up-regulated miR-182 expression in breast cancer cells. Inhibition or knockdown of β-catenin significantly reduced miR-182 level in MDA-MB-231 cells. Chromatin immunoprecipitation assay confirmed the constitutive binding of β-catenin on miR-182 promoter. We further identified the tumor suppressor Reversion-inducing Cysteine-rich Protein with Kazal motifs (RECK) as a new target of miR-182. Anti-miR-182 increased RECK protein in MDA-MB-231 cells while pre-miR-182 reduced RECK protein but not mRNA in H184B5F5/M10 human normal mammary epithelial cells. Restoration of RECK protein by anti-miR-182 attenuated matrix metalloproteinase-9 (MMP-9) activity, cell invasion and colony formation. More importantly, ectopic expression of miR-182 inhibited restoration of RECK protein by β-catenin inhibitor indicating induction of miR-182 is important for β-catenin-induced down-regulation of RECK. Taken together, we provide evidences that miR-182 is up-regulated by β-catenin signaling pathway in breast cancer and its up-regulation increases MMP-9 activity and cell invasiveness by repressing RECK.
    Advisory Committee
  • Yeou-Lih Huang - chair
  • Te-Hsiu Lee - co-chair
  • Kuang-hung Cheng - co-chair
  • Jau-Shyang Huang - co-chair
  • Wen- chun Hung - advisor
  • Files
  • etd-0624113-191725.pdf
  • Indicate in-campus at 1 year and off-campus access at 1 year.
    Date of Submission 2013-07-24

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