Abstract
BackgroundRecent 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.ResultsZMYND10 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.ConclusionsResults 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.
Highlights
Recent studies suggested that ZMYND10 is a potential tumor suppressor gene in multiple tumor types
We found that ZMYND10 suppresses breast cancer tumorigenicity through upregulating miR145-5p to inhibit the expression of oncogene NEDD9, which results in suppression of cell invasion and migration and breast cancer progression
ZMYND10 downregulation in breast cancer is associated with poor patient survival To investigate whether ZMYND10 is downregulated in breast cancer, we first used immunohistochemistry assay to examine its expression in tumor-adjacent (n = 16) and tumor tissues (n = 27)
Summary
Recent studies suggested that ZMYND10 is a potential tumor suppressor gene in multiple tumor types. The mechanism by which ZMYND10 inhibits breast cancer remains unclear. We investigated the role and mechanism of ZMYND10 in breast cancer inhibition. Clinical challenges in the treatment of breast cancer patients remain and it is ZMYND10, known as BLU (zinc finger, MYNDtype containing 10), encodes a 50-kD protein containing an MYND-type zinc finger DNA-binding domain in the C-terminus that is commonly found in transcription repressors [4]. In recent decades, documented studies have confirmed that ZMYND10 is a tumor suppressor that can induce apoptosis [8, 15], arrest cell cycle [16], and inhibit proliferation and angiogenesis [17] in different tumors.
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