Triple negative breast cancer (TnBc) is one of the most aggressive types of breast cancer and has a poor prognosis. Therefore, the development of novel drugs and understanding the molecular mechanisms that may contribute to the initiation and development of TnBc are urgently required. chidamide, a histone deacetylase inhibitor, has been reported as possessing anti-cancer properties in several cancers, however, the function of chidamide in TnBc remains to be elucidated. The present study revealed that chidamide inhibited the proliferation, colony formation and migration of TnBc cells. experiments investigating the underlying mechanism revealed that chidamide upregulated the expression of microrna (mir)-33a-5p in TnBc cells via rT-qPcr. luciferase reporter assay demonstrated that mir-33a-5p was bound to the 3'-untranslated region of lactate dehydrogenase a (ldHa) and decreased the expression of ldHa in TnBc cells. in addition, chidamide suppressed the expression of LDHA and significantly decreased the glycolysis of TNBC cells. collectively, the results of the present study demonstrated that chidamide reprogramed glucose metabolism, partially by targeting the mir-33a-5p/ldHa pathway, in TnBc. These findings indicate that chidamide may be a promising novel drug in the treatment of patients with TnBc.
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor outcome. The discovery that dysregulated microRNAs (miRNAs) play an important role in tumor progression has led to the suggestion that miRNAs (miRs) could be a potential target for the treatment of TNBC. In the present study, it was demonstrated that miR-598 expression was significantly decreased in TNBC tissues and was related to the degree of lymph node metastasis of patients with TNBC. Ectopic expression of miR-598 suppressed viability and colony formation, as well as increased the apoptosis of TNBC cells. To further understand the functional mechanism of action underlying miR-598 in TNBC, targets of miR-598 were predicted with the miRDB bioinformatics tool. Jagged 1 (JAG1) was identified as a direct target of miR-598, possessing a binding site for miR-598 in its 3'-untranslated region. Overexpression of miR-598 inhibited the expression of JAG1 in TNBC cells. In addition, JAG1 was highly expressed in TNBC tissues and its expression was negatively correlated with the expression of miR-598. Overexpression of JAG1 significantly attenuated the inhibitory effects of miR-598 on the proliferation and colony formation of TNBC cells. Collectively, these results provided novel insights into the functional mechanism of action for the miR-598/JAG1 pathway in the development of TNBC.
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