Up-regulation of HDAC9 promotes cell proliferation through suppressing p53 transcription in osteosarcoma.

Abstract

Increasing studies have demonstrated that altered expression of histone deacetylases (HDACs) plays a critical role in the tumorigenesis through up-regulation or down-regulation of key genes involved in cell proliferation, cell-cycle regulation and apoptosis. In the present study, the expression and function of HDAC9 were investigated in osteosarcoma. Quantitative real-time PCR and Western blot analysis found that HDAC9 was up-regulated in osteosarcoma tissues, when compared with that in adjacent normal tissues. In vitro studies further demonstrated that overexpression of HDAC9 in U2OS and MG63 cells promoted cell proliferation and invasion. Using chromatin immunoprecipitation (ChIP) assay, we found that HDAC9 epigenetically repressed p53 transcription through binding to its proximal promoter region. Therefore, our data suggest an important role for HDAC9/p53 regulatory pathway in the osteosarcoma progression.