作者: Kousuke Watanabe , Yosuke Amano , Rie Ishikawa , Mitsuhiro Sunohara , Hidenori Kage
DOI: 10.1002/CAM4.505
关键词: Cancer epigenetics 、 Molecular biology 、 Cancer research 、 Histone methylation 、 Ectopic expression 、 Metastasis 、 Cancer 、 DNA methylation 、 Biology 、 microRNA 、 Histone H3
摘要: MicroRNA expression is frequently altered in human cancers, and some microRNAs act as oncogenes or tumor suppressors. MiR-139-5p (denoted thereafter miR-139) has recently been reported to function a suppressor several types of cancer (hepatocellular carcinoma, colorectal cancer, breast gastric cancer), but its non-small-cell lung (NSCLC) the mechanism suppression have not studied detail. MiR-139 was suppressed primary NSCLCs. located within intron PDE2A significantly correlated with PDE2A. A chromatin immunoprecipitation assay revealed that miR-139 epigenetically silenced by histone H3 lysine 27 trimethylation (H3K27me3) host gene this process independent promoter DNA methylation. Pharmacological inhibition both methylation deacetylation-induced Ectopic cell lines did affect proliferation nor migration invasion through extracellular matrix. In NSCLCs, decreased associated distant lymph node metastasis histological invasiveness (lymphatic vascular invasion) on univariate multivariate analyses. Collectively, these results suggest H3K27me3-mediated silencing enhances an invasive metastatic phenotype NSCLC.