Effects of SB939 are mediated by STAT3 to inhibit breast cancer cell metastasis-related genes.

The histone deacetylase inhibitor pracinostat (SB939) may inhibit metastasis of triple-negative breast cancer by downregulating fibronectin (FN1) expression through the STAT3 signaling pathway. SB939 exhibits low cytotoxicity and is a potential targeted agent against breast cancer. The present study investigated the value of STAT3 and FN1 as breast cancer treatment targets and integrated cancer databases and bioinformatics tools to evaluate the effect of SB939 on breast cancer metastasis. Gene Set Enrichment Analysis, Gene Expression Profiling Interactive Analysis, Gene Expression Database of Normal and Tumor Tissues 2, The University of Alabama at Birmingham Cancer data analysis portal, GeneMANIA, Search Tool for the Retrieval of Interacting Genes/Proteins, LinkedOmics and Tumor Immune Estimation Resource databases were used in the present study. SB939 inhibited enrichment of the STAT3 pathway and decreased the expression of FN1. FN1 and STAT3 expression was markedly higher in breast cancer tissues compared with normal tissues. Kaplan-Meier curves demonstrated that increased expression of STAT3 and FN1 was associated with low survival in patients with breast cancer with overall, recurrence-free and disease-specific survival and FN1 having the strongest association with MMP2, which facilitating extracellular matrix degradation and metastatic niche formation. Furthermore, MMP2 exhibits crosstalk STAT3 to induce metastasis of breast cancer cells. To conclude, SB939 may be used as a small molecule compound for the clinical treatment of breast cancer.