Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. In the absence of effective molecular markers for TNBC, there is an urgent clinical need for promising therapeutic target for TNBC. Histone deacetylases (HDACs), key regulators for chromatin remodeling and gene expression, have been suggested to play critical roles in cancer development. However, little is known ~the functions and implications of HDACs in TNBC treatment in the future. By analyzing the expression and prognostic significance of HDAC family members in TNBC through TCGA and METABRIC databases, HDAC7 was found to be downregulated in TNBC samples and the survival of patients with lower expression of HDAC7 was shorter. Furthermore, HDAC7 was negatively associated with NudC domain containing 1 (NudCD1) and γ-glutamyl hydrolase (GGH). Loss of NudCD1 or GGH predicted improved overall survival time (OS) of patients with TNBC. In vitro experiments showed that silencing of HDAC7 enhanced TNBC cell proliferation, while overexpression HDAC7 inhibited TNBC cell proliferation. The results of functional experiments confirmed that HDAC7 negatively modulated GGH and NudCD1 expression. Furthermore, decrease of NudCD1 or GGH inhibited cell proliferation. Notably, the HDAC7-NudCD1/GGH axis was found to be associated with NK cell infiltration. Overall, the present study revealed a novel role of HDAC7-NudCD1/GGH axis in TNBC, which might provide a promising treatment strategy for patients with TNBC.
Keywords: NudC domain containing 1; histone deacetylase 7; triple negative breast cancer; γ-glutamyl hydrolase.
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