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ZMYND10, an epigenetically regulated tumor suppressor, exerts tumor-suppressive functions via miR145-5p/NEDD9 axis in breast cancer
- 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.
- Subjects :
- ZMYND10
0301 basic medicine
Tumor suppressor gene
Down-Regulation
Breast Neoplasms
Biology
NEDD9
Epigenesis, Genetic
03 medical and health sciences
Mice
Breast cancer
0302 clinical medicine
Cell Movement
Cell Line, Tumor
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
Promoter Regions, Genetic
Molecular Biology
Genetics (clinical)
Adaptor Proteins, Signal Transducing
Cell Proliferation
Cell growth
Research
miR145-5p
Cell migration
DNA Methylation
medicine.disease
Gene Expression Regulation, Neoplastic
Cytoskeletal Proteins
MicroRNAs
030104 developmental biology
Apoptosis
030220 oncology & carcinogenesis
Cancer research
MCF-7 Cells
Ectopic expression
Female
Signal transduction
Neoplasm Transplantation
Developmental Biology
Subjects
Details
- ISSN :
- 18687083
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Clinical epigenetics
- Accession number :
- edsair.doi.dedup.....d8e00c81a2cd6b3b3bae87d304dff8ea