KDM6A regulates cell proliferation, invasion and apoptosis by transcriptional inhibits p16ink4a

Lysine demethylase 6A (KDM6A) plays a crucial function in several cancers. However, there is little known about the function of KDM6A in gastric cancer. Here, we found that KDM6A expression level was obviously higher in gastric tissues and cells, compared with normal tissues and normal gastric mucosal cells. In addition, the expression of KDM6A was correlated with tumor size, metastasis, tumor stage and poor prognosis. Cell apoptosis assay suggested that KDM6A suppressed cell apoptosis under challenged with or without VP-16 (etoposide). Colony formation assay and CCK-8 assay suggested that knockdown of KDM6A suppressed cell proliferation, and cell cycle progression assay demonstrated that knockdown of KDM6A arrested cell at G(0)/G(1) phase. On the contrary, over expression of KDM6A promoted cell proliferation through facilitated cell G(1)/S phase transition. To further investigate the mechanism KDM6A contributed of the cell cycle progression, western blot, ChIP assay and luciferase reporter assay suggested that KDM6A transcriptional inhibited p16(ink4a). Furthermore, KDM6A improved the ability of CTC-141 and MKN45 cells metastasis and anchorage-independent growth. These data demonstrated that KDM6A might serve as an oncogene, promote gastric cancer cells proliferation through transcriptional inhibition of p16ink4a, KDM6A also suppressed cell apoptosis, but the detail mechanism was unknown.