Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Clinical Laboratory Sciences and Medical Biotechnology / 醫學檢驗暨生物技術學系所
  4. miRNA-34b as a tumor suppressor in estrogen-dependent growth of breast cancer cells
 
  • Details

miRNA-34b as a tumor suppressor in estrogen-dependent growth of breast cancer cells

Journal
Breast Cancer Research
Journal Volume
13
Journal Issue
6
Date Issued
2011
Author(s)
Lee Y.-M.
Lee J.-Y.
CHAO-CHI HO  
Hong Q.-S.
SUNG-LIANG YU  
Tzeng C.-R.
PAN-CHYR YANG  
HUEI-WEN CHEN  
DOI
10.1186/bcr3059
URI
https://scholars.lib.ntu.edu.tw/handle/123456789/502890
Abstract
Introduction: Estrogen is involved in several physiological and pathological processes through estrogen receptor (ER)-mediated transcriptional gene regulation. miRNAs (miRs), which are noncoding RNA genes, may respond to estrogen and serve as posttranscriptional regulators in tumorigenic progression, especially in breast cancer; however, only limited information about this possibility is available. In the present study, we identified the estrogen-regulated miR-34b and investigated its functional role in breast cancer progression.Methods: Estrogen-regulated miRNAs were identified by using a TaqMan low density array. Our in vivo Tet-On system orthotopic model revealed the tumor-suppressive ability of miR-34b. Luciferase reporter assays and chromatin immunoprecipitation assay demonstrated miR-34b were regulated by p53-ER interaction.Results: In this study, we identified one such estrogen downregulated miRNA, miR-34b, as an oncosuppressor that targets cyclin D1 and Jagged-1 (JAG1) in an ER+/wild-type p53 breast cancer cell line (MCF-7), as well as in ovarian and endometrial cells, but not in ER-negative or mutant p53 breast cancer cell lines (T47D, MBA-MB-361 and MDA-MB-435). There is a negative association between ERα and miR-34b expression levels in ER+ breast cancer patients. Tet-On induction of miR-34b can cause inhibition of tumor growth and cell proliferation. Also, the overexpression of miR-34b inhibited ER+ breast tumor growth in an orthotopic mammary fat pad xenograft mouse model. Further validation indicated that estrogen's inhibition of miR-34b expression was mediated by interactions between ERα and p53, not by DNA methylation regulation. The xenoestrogens diethylstilbestrol and zeranol also showed similar estrogenic effects by inhibiting miR-34b expression and by restoring the protein levels of the miR-34b targets cyclin D1 and JAG1 in MCF-7 cells.Conclusions: These findings reveal that miR-34b is an oncosuppressor miRNA requiring both ER+ and wild-type p53 phenotypes in breast cancer cells. These results improve our ability to develop new therapeutic strategies to target the complex estrogenic pathway in human breast cancer progression through miRNA regulation. ? 2011 Lee et al.; licensee BioMed Central Ltd.
SDGs

[SDGs]SDG3

Other Subjects
cyclin D1; diethylstilbestrol; estrogen; estrogen receptor alpha; Jagged1; luciferase; microRNA; microRNA 34b; protein p53; tumor suppressor protein; unclassified drug; zeranol; antineoplastic hormone agonists and antagonists; calcium binding protein; cyclin D1; estrogen; estrogen receptor; membrane protein; microRNA; MIRN34 microRNA, human; protein p53; Serrate proteins; signal peptide; tamoxifen; adult; aged; animal experiment; animal model; article; breast cancer; cancer cell; cancer growth; cancer inhibition; carcinogenesis; cell proliferation; chromatin immunoprecipitation; clinical article; controlled study; DNA methylation; down regulation; endometrium cell; estrogen activity; female; human; human cell; in vivo study; mouse; nonhuman; ovary cell; animal; biological model; breast tumor; cancer staging; drug effect; drug screening; gene expression; gene expression profiling; genetics; metabolism; middle aged; mouse mutant; nude mouse; pathology; tumor cell line; tumor suppressor gene; Adult; Aged; Animals; Antineoplastic Agents, Hormonal; Breast Neoplasms; Calcium-Binding Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Estrogens; Female; Gene Expression; Gene Expression Profiling; Genes, Tumor Suppressor; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Mice; Mice, Nude; Mice, SCID; MicroRNAs; Middle Aged; Models, Biological; Neoplasm Staging; Receptors, Estrogen; Tamoxifen; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science