| URN |
etd-0624113-191725 |
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| Author |
Chi-Hsiang Chiang |
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| Author's Email Address |
No Public. |
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| Statistics |
This thesis had been viewed 5572 times. Download 439 times. |
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| Department |
Institute of Biomedical Sciences |
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| Year |
2012 |
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| Semester |
2 |
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| Degree |
Ph.D. |
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| Type of Document |
|
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| Language |
English |
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| Title |
Regulation of microRNA-182 and its functional role in breast cancer |
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| Date of Defense |
2013-07-12 |
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| Page Count |
103 |
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| Keyword |
RECK
β-catenin
microRNA
matrix metalloproteinase
|
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| 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. |
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| 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
|
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| Files |
Indicate in-campus at 1 year and off-campus access at 1 year. |
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| Date of Submission |
2013-07-24 |
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