Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14

The objective of this study is as follows. Inhibitor of growth (ING) 4 is a novel member of the ING family. It has been thought to play an inhibitory role in several malignancies through its involvment in gene transcription, apoptosis, cell cycle control, and tumor angiogenesis. The involvement of ING4 in melanomagenesis remains unknown. The purpose of this study was to investigate the inhibitory effects of ING4 on melanoma and its mechanisms. The method used was to construct recombinant plasmid pcDNA3.1-ING4 and transfect it into the human melanoma cell line M14. The effects and mechanisms of ING4 on proliferation and apoptosis of M14 cells were analyzed in vitro according to MTT assay, colony formation assay, and TUNEL assay. The detection of the expression of cell cycle or apoptosis regulators in transfected M14 cells was carried out by western blot analysis. Moreover, the level of ING4 in melanoma tissues was examined by immunohistochemistry. The expression of ING4 was markedly reduced in cutaneous melanoma tissues. Overexpression of ING4 could induce growth suppression and apoptosis enhancement in M14 cells, and also induce the upregulation of p27, Bax and Cyt-c, and the downregulation of cyclinD1, SKP2, Bcl-2, and caspase-3. In conclusion, ING4, as a novel tumor suppressor, has a potential role in growth suppression and apoptosis enhancement of melanoma M14 through the activation of the mitochondrial-induced apoptotic pathway and the hindrance of cell cycle progression. The deregulation of ING4 might be involved in melanomagenesis.