Epigenetic reprogramming of human lung cancer cells with the extract of bovine parthenogenetic oocytes. Issue 9 (30th May 2014)

• Record Type: Journal Article
• Authors: Wang, Zhenfei; Dao, Rinuo; Bao, Luri; Dong, Yanhua; Wang, Haiyang; Han, Pengyong; Yue, Yongli; Yu, Haiquan
• Is Part Of: Journal of cellular and molecular medicine. Volume 18:Issue 9(2014)
• Page Start: 1807
• Page End: 1815
• Publication Date: 2014-05-30
• Subjects: Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.12306
• Languages: English
• ISSNs: 1582-1838

Abstract

<abstract abstract-type="main" id="jcmm12306-abs-0001"> <title>Abstract</title> <p>The tumour suppressor gene silencing and proto‐oncogene activation caused by epigenetic alterations plays an important role in the initiation and progression of cancer. Re‐establishing the balance between the expression of tumour suppressor genes and proto‐oncogenes by epigenetic modulation is a promising strategy for cancer treatment. In this study, we investigated whether cancer cells can be epigenetically reprogrammed by oocyte extract. H460 human lung cancer cells were reversibly permeabilized and incubated with the extract of bovine parthenogenetic oocytes. Bisulphite sequencing showed that bovine parthenogenetic oocyte extract induced significant demethylation at the promoters of the tumour suppressor genes <italic>RUNX3</italic> and <italic>CDH1</italic>, but not at the promoter of the oncogenic pluripotency gene <italic>SOX2</italic>. Chromatin immunoprecipitation showed that the histone modifications at <italic>RUNX3</italic> and <italic>CDH1</italic> promoters were modulated towards a transcriptionally activating state, while those at <italic>SOX2</italic> promoter towards a transcriptionally repressive state. Correspondingly, bovine parthenogenetic oocyte extract reversed the epigenetic silencing of <italic>RUNX3</italic> and <italic>CDH1</italic>, and repressed the expression of <italic>SOX2</italic>. At the functional level, proliferation, anchorage‐independent growth, migration and invasion of H460 cells was strongly inhibited. These results indicate that bovine parthenogenetic oocyte extract changes the expression patterns of tumour suppressor and oncogenic genes in cancer cells by remodelling the epigenetic modifications at their promoters. Bovine parthenogenetic oocyte extract may provide a useful tool for epigenetically reprogramming cancer cells and for dissecting the epigenetic mechanisms involved in tumorigenesis.</p> </abstract>