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ZMYND10,an epigenetically regulated tumor suppressor,exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer

Wang  Yan  Dan  Liangying  Li  Qianqian  Li  Lili  Zhong  Lan  Shao  Bianfei  Yu  Fang  He  Sanxiu  Tian  Sha orong  He  Jin  Xiao  Qian  Putti  ThomasC  He  Xiaoqian  Feng  Yixiao  Lin  Yong  Xiang  Tingxiu  
【摘要】:Background:Recent studies suggested that ZMYND10 is a potential tumor suppressor gene in multiple tumor types.However,the mechanism by which ZMYND10 inhibits breast cancer remains unclear.Here,we investigated the role and mechanism of ZMYND10 in breast cancer inhibition.Results:ZMYND10 was dramatically reduced in multiple breast cancer cell lines and tissues,which was associated with promoter hypermethylation.Ectopic expression of ZMYND10 in silenced breast cancer cells induced cell apoptosis while suppressed cell growth,cell migration and invasion in vitro,and xenograft tumor growth in vivo.Furthermore,molecular mechanism studies indicated that ZMYND10 enhances expression of miR145-5 p,which suppresses expression of NEDD9 protein through directly targeting the 3'-untranslated region of NEDD9 mRNA.Conclusions:Results from this study shows that ZMYND10 suppresses breast cancer tumorigenicity by inhibiting the miR145-5 p/NEDD9 signaling pathway.This novel discovered signaling pathway may be a valid target for small molecules might help to develop new therapies to better inhibit the breast cancer metastasis.

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