Histone Deacetylase Inhibitors inhibit lung adenocarcinoma metastasis via HDAC2/YY1 mediated downregulation of Cdh1

Abstract

Metastasis leads to high mortality of lung adenocarcinoma patients. Histone deacetylases are reliable targets of anti-tumor drugs, and histone deacetylase inhibitors (HDACi) have become a hot field of anti-tumor drug research. However, the specific mechanisms by which HDACi inhibits lung cancer metastasis have not been fully elucidated. Here, we detected the role of HDACi and HDAC2/YY1 in the process of lung adenocarcinoma migration by qPCR, immunobloting, co-immunoprecipitation, chromatin-immunoprecipitation and cell migration assay, combined with online database analysis. We found both trichostatin A (TSA) and sodium butyrate (NaBu) inhibit lung cancer cell invasion and migration significantly via Histone Deacetylase 2 (HDAC2). HDAC2 overexpression promotes lung cancer cell migration, while shHDAC2 inhibits lung cancer cell migration obviously. Further investigation show that HDAC2 interacts with YY1 and deacelytes Lycine 27 of Histone 3 to inhibits Cdh1 transcriptional activity and then promotes cell migration. This study revealed a new functional mechanism of HDAC2/YY1 in lung adenocarcinoma cell migration.