title: Specific reversal of tumor-suppressor gene promoter hypermethylation with bovine oocyte extract.
abstract: Epigenetic silencing of tumor-suppressor genes by promoter hypermethylation contributes considerably to the initiation and progression of cancer. Nucleoside analogs, the most widely used DNA methylation inhibitors, have the drawbacks of inducing repetitive sequence hypomethylation. Here, we aimed to specifically reverse tumor-suppressor gene (TSG) promoter hypermethylation with bovine oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with bovine oocyte extract for 3.5 h. The extract treatment led to significant demethylation of the hypermethylated promoters of the TSGs RUNX3, CDH1, RASSF1A and WIF1; however, the methylation levels of repetitive sequences were not affected. The promoter demethylation induced by bovine oocyte extract substantially upregulated the expression of RUNX3, CDH1, RASSF1A and WIF1, and significantly inhibited the anchorage-independent proliferation, migration and invasion of H460 cells. This study demonstrates that bovine oocyte extract can reverse the malignant phenotype by serving as an efficient and safe DNA demethylator. The active demethylation activity of bovine oocyte extract is valuable for dissecting the epigenetic alterations in cancer cells and developing novel safe anticancer drugs based on epigenetic mechanisms.
authors.affiliation: The Key Laboratory of Mammal Reproductive Biology and Biotechnology, Ministry of Education, Inner Mongolia University, Huhhot 010021, P.R. China.
authors.forename: Zhenfei
authors.initials: Z
authors.lastname: Wang
authors.forename: Haixia
authors.initials: H
authors.lastname: Gao
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Ren
authors.forename: Luri
authors.initials: L
authors.lastname: Bao
authors.forename: Rula
authors.initials: R
authors.lastname: Sa
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Haidong
authors.initials: H
authors.lastname: Bai
authors.forename: Haiquan
authors.initials: H
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms; D009361:Neoplasm Invasiveness / Q000235:genetics; D009865:Oocytes / Q000166:cytology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014020:Tissue Extracts / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D050677:Core Binding Factor Alpha 3 Subunit; C411762:RASSF1 protein, human; D012097:Repressor Proteins; C493729:Runx3 protein, human; D014020:Tissue Extracts; D025521:Tumor Suppressor Proteins; C485569:WIF1 protein, human