國家衛生研究院 NHRI:Item 3990099045/10961
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10961


    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
    Authors: Huang, WT;Tsai, YH;Chen, SH;Kuo, CW;Kuo, YL;Lee, KT;Chen, WC;Wu, PC;Chuang, CY;Cheng, SM;Lin, CH;Leung, EY;Chang, YC;Cheung, CHA
    Contributors: National Institute of Cancer Research
    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.
    Date: 2017-12-13
    Relation: Frontiers in Pharmacology. 2017 Dec 13;8(DEC):Article number 902.
    Link to: http://dx.doi.org/10.3389/fphar.2017.00902
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1663-9812&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000417795300001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85037735803
    Appears in Collections:[Shang-Hung Chen] Periodical Articles

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