UHRF1-mediated tumor suppressor gene inactivation in nonsmall cell lung cancer.

摘要: BACKGROUND: The UHRF1 gene possesses an essential role in DNA methylation maintenance, but its contribution to tumor suppressor hypermethylation primary human cancers currently remains unclear. METHODS: mRNA expression levels of UHRF1, DNMT1, DNMT3A, DNMT3B, and E2F1 were evaluated 105 nonsmall cell lung carcinomas by quantitative polymerase chain reaction. The status CDKN2A RASSF1 promoters was examined pyrosequencing. knocked down short hairpin RNA A549 adenocarcinoma cells. RESULTS: All 4 genes overexpressed a coordinated manner the tissues, their correlated with that E2F1. Higher tissues (P = .005) .034), relationship combined epigenotype even stronger 2.3 × 10−4). When cells, lower RASSF1, CYGB, CDH13 observed. Also, knockdown clones demonstrated reduced proliferation decreased migration properties. CONCLUSIONS: Our data demonstrate is key epigenetic switch, which controls cycle carcinoma through ability sustain transcriptional silencing maintaining hypermethylated status. Thus, should be considered, along DNMTs, among potential targets for cancer treatment and/or therapeutic stratification. Cancer 2011. © 2010 American Society.