HDAC1 mediates epithelial-mesenchymal transition and promotes cancer cell invasion in glioblastoma.

Abstract

Glioblastoma multiforme (GBM) is one of the most malignant tumors of the central nervous system, and its treatment has always been a difficult clinical problem. Here, we evaluated HDAC1 expression patterns and their effect on prognosis based on GBM cases from TCGA and CGGA databases. Expression was compared between GBM samples and normal controls. High HDAC1 expression was found to be an indicator of poor prognosis in glioblastoma. We also established a protein-protein interaction network to explore HDAC1-related interacting proteins, including the epithelial-mesenchymal transition (EMT)-related protein VIM, which is closely associated with HDAC1. Consistently, functional enrichment analysis showed that several GBM tissues with high HDAC1 were enriched in the expression of cancer markers, such as those involved in glycolysis, hypoxia, inflammation, and some signaling pathways. Next, this study analyzed the effect of HDAC1 on invasive ability and the EMT signaling pathway in GBM cells in vitro. The results showed that an HDAC1 inhibitor (RGFP109) could inhibit the EMT process in glioma cells in vitro, thereby affecting the invasion and migration of cells. Similar results were obtained based on in vivo studies. Our data suggest that HDAC1 has the potential to be a powerful prognostic biomarker, which might provide a basis for developing therapeutic targets for GBM.