Abstract 78: Epigenetic regulation of the metastatic progression of non-small cell lung cancer by the histone H3K9 methyltransferase SETDB1

Abstract

Abstract Aberrant histone methylation is contributes to tumor development and progression by histone methyltransferase. SETDB1 is an authentic H3K9 methyltransferase that contributes to the epigenetic silencing of target genes in cancer cells, but the role of SETDB1 function in mediating tumor metastasis has not been reported. We show here that H3K9Me2 and SETDB1 are down-regulated in metastatic lung cancer cell lines. Ectopic expression of SETDB1 in highly invasive lung cancer cells suppressed cancer cell migration, invasion and filopodia formation. In contrast, knockdown of endogenous SETDB1 in non-invasive lung cancer cells by RNA interference increases cell migration and invasion in vitro. Mechanistic investigations suggested that SETDB1 is specifically down-regulated by miR-29b in metastatic lung cancer cells. Ectopic miR-29b expression in non-invasion lung cancer cells increases cell invasion ability. These results indicate that SETDB1 contributes to the repressive role and concomitant dysregulation of epigenetic pathways in lung cancer progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 78. doi:10.1158/1538-7445.AM2011-78