Histone deacetylase in human sarcomas

Increasing evidence showed that altered histone deacetylases (HDACs) are involved in, and exert cell type specific roles in sarcomagenesis. Here we reviewed expression and roles of HDACs in several types of human sarcomas, providing a basic guideline for personalized therapy. In sarcomas, overexpression of HDACs was common, including a prevalence in uterine sarcomas. Class I HDAC1-3, especially HDAC1-2, were upregulated in most sarcomas and were often associated with poor prognosis. Class I HDACs inhibit tumor suppressor expression and lineage differentiation, but maintain chromatin integrity and oncofusion protein stability. Class II HDACs have specific functions in cellular transformation, long telomeres maintenance, drug resistance, and cytoskeletal organization, and act as negative predictors in some sarcomas; for example, HDAC4 for leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), HDAC5 for uterine LMS, HDAC6 for ESS, chondrosarcoma (CHS) and undifferentiated endometrial sarcoma. Moreover, some HDACs play dual, cell-context or cellular localization-dependent roles. HDAC2 and HDAC5 could promote or suppress osteosarcoma growth. HDAC4 acts as a tumor suppressor in CHS but as an oncogene in other sarcomas. Moreover, HDAC4 is the targets of several microRNAs in osteosarcoma. Cytoplasmic HDAC6 increases self-renewal and cell migration, compared with nuclear HDAC6 enhancing EWSR1-FLI1 transcription. Thus, the diverse expression and roles of HDACs in sarcoma pathogenesis will be a solid foundation to guide personalized therapeutic application of HDAC modulators in sarcomas.