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.

中文翻译：

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ZMYND10 是一种表观遗传调控的肿瘤抑制因子，通过 miR145-5p/NEDD9 轴在乳腺癌中发挥肿瘤抑制功能。

背景最近的研究表明，ZMYND10是多种肿瘤类型中潜在的抑癌基因。然而，ZMYND10抑制乳腺癌的机制仍不清楚。在这里，我们研究了 ZMYND10 在乳腺癌抑制中的作用和机制。结果 ZMYND10 在多种乳腺癌细胞系和组织中显着减少，这与启动子高甲基化有关。ZMYND10 在沉默的乳腺癌细胞中的异位表达诱导细胞凋亡，同时抑制细胞生长、体外细胞迁移和侵袭，以及体内异种移植肿瘤的生长。此外，分子机制研究表明，ZMYND10 可增强 miR145-5p 的表达，而 miR145-5p 通过直接靶向 NEDD9 mRNA 的 3'-非翻译区来抑制 NEDD9 蛋白的表达。结论 本研究结果表明，ZMYND10 通过抑制 miR145-5p/NEDD9 信号通路来抑制乳腺癌的致瘤性。这种新发现的信号通路可能是小分子的有效靶点，可能有助于开发新疗法以更好地抑制乳腺癌转移。