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

Authors :
Yong Lin
Qian Xiao
Yan Wang
Fang Yu
Xiaoqian He
Lan Zhong
Qianqian Li
Sanxiu He
Shaorong Tian
Jin He
Lili Li
Bianfei Shao
Yixiao Feng
Thomas C. Putti
Liangying Dan
Tingxiu Xiang
Source :
Clinical Epigenetics
Publication Year :
2019

Abstract

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 miR145-5p, which suppresses the expression of NEDD9 protein through directly targeting the 3'-untranslated region of NEDD9 mRNA. Conclusions Results from this study show that ZMYND10 suppresses breast cancer tumorigenicity by inhibiting the miR145-5p/NEDD9 signaling pathway. This novel discovered signaling pathway may be a valid target for small molecules that might help to develop new therapies to better inhibit the breast cancer metastasis.

Details

ISSN :
18687083
Volume :
11
Issue :
1
Database :
OpenAIRE
Journal :
Clinical epigenetics
Accession number :
edsair.doi.dedup.....d8e00c81a2cd6b3b3bae87d304dff8ea