HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells.

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dc.contributor.author Huang, Wen-Tsung en
dc.contributor.author Tsai, Yu-Hsuan en
dc.contributor.author Chen, Shang-Hung en
dc.contributor.author Kuo, Ching-Wen en
dc.contributor.author Kuo, Yao-Lung en
dc.contributor.author Lee, Kuo-Ting en
dc.contributor.author Chen, Wen-Chung en
dc.contributor.author Wu, Pei Chih en
dc.contributor.author Chuang, Chun-Yu en
dc.contributor.author Cheng, Siao Muk en
dc.contributor.author Lin, Chun-Hui en
dc.contributor.author Leung, Yee Fun en
dc.contributor.author Chang, Yung-Chieh en
dc.contributor.author Cheung, Chun Hei Antonio en
dc.date.accessioned 2018-11-22T02:32:47Z en
dc.date.issued 2017-01 en
dc.identifier.issn 1663-9812 en
dc.identifier.uri http://hdl.handle.net/2292/44571 en
dc.description.abstract Intrinsic or acquired resistance to hormone therapy is frequently reported in estrogen receptor positive (ER+) breast cancer patients. Even though dysregulations of histone deacetylases (HDACs) are known to promote cancer cells survival, the role of different HDACs in the induction of hormone therapy resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro-tumor survival molecule and miR-125a-5p is a recently discovered tumor suppressor. In this study, we found that ER+, hormone-independent, tamoxifen-resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and survivin, but show decreased expression of miR-125a-5p, as compared to the parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p, increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and restored the sensitivity to tamoxifen. The same treatments also further increased the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1 breast cancer cells in vitro. Kaplan-Meier analysis and receiver operating characteristic curve analysis of expression cohorts of breast tumor showed that high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5 positively modulates the expression of survivin, and negatively regulates the expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells. These findings indicate that dysregulations of HDAC2 and HDAC5 promote the development of hormone independency and tamoxifen resistance in ERC breast cancer cells in part through expression regulation of survivin and miR-125a-5p. en
dc.format.medium Electronic-eCollection en
dc.language eng en
dc.relation.ispartofseries Frontiers in pharmacology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1663-9812/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.title HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells. en
dc.type Journal Article en
dc.identifier.doi 10.3389/fphar.2017.00902 en
pubs.begin-page 902 en
pubs.volume 8 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 29326587 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype research-article en
pubs.subtype Journal Article en
pubs.elements-id 719924 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Auckland Cancer Research en
dc.identifier.eissn 1663-9812 en
pubs.record-created-at-source-date 2018-01-13 en
pubs.dimensions-id 29326587 en

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