Histone deacetylase inhibitors differentially regulate c-Myc expression in retinoblastoma cells.

Abstract

Retinoblastoma (RB) is the most prevalent childhood intraocular cancer type. Previous studies have demonstrated that c-myc (a proto-oncogene) is associated with tumorigenesis. However, at present, the influence of the expression profile and bioactivity of c-Myc on RB occurrence and progression is yet to be characterised. Notably, the present study demonstrated that c-myc is downregulated in the RB cell line WERI-Rb1. However, treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was revealed to significantly upregulate the expression of c-Myc mRNA and protein in WERI-Rb1 cells. Moreover, TSA increased the activity of the c-myc promoter in WERI-Rb1 cells, and the expression of c-Myc was also regulated by other HDAC inhibitors, including vorinostat (SAHA), valproic acid sodium salt (VPA) and entinostat. Notably, although c-myc was silenced in the Y79 cell line, the HDAC inhibitor TSA did not induce upregulation of mRNA and protein in Y79 cells. By contrast, certain HDAC inhibitors (TSA, VPA and SAHA) were discovered to significantly decrease the activity of the c-myc promoter in Y79 cells. Furthermore, the current data indicated that exogenous c-myc expression has a mild inhibitory effect on WERI-Rb1 and Y79 cell viability. Therefore, the present study revealed novel insights into the expression mechanism and bioactivity of c-Myc in RB cells.