Transcriptomics

Dataset Information

30

Epigenetic Reprogramming Modulates Malignant Properties of Human Liver Cancer Cells


ABSTRACT: Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. In this context we have addressed the impact of epigenetic alterations and local microenvironment on the functional and transcriptional reprogramming of hepatic cancer stem cells. (CSCs) using the DNMT1 inhibitor Zebularine (ZEB). We show for the first time that cellular context is a critical determinant in the response to DNMT1 inhibition resulting in either a long term epigenetically driven malignant reprogramming or an effective antitumor therapeutic reprogramming. Furthermore, permanent reduction of DNMT1 protein level renders the HCC cell lines insensitive to both DNMT1 inhibition and cellular context. These results emphasize the importance of decoding the mechanisms involved in therapeutic application of DNA demethylating agents. Huh7 and PLC treated with ZEB, and Huh7 depleted for DNMT1

ORGANISM(S): Homo sapiens  

SUBMITTER: Snorri S Thorgeirsson  Daekwan Seo   Chiara Raggi   Snorri S. Thorgeirsson    

PROVIDER: E-GEOD-47932 | ArrayExpress| 2014-06-03

SECONDARY ACCESSION(S): GSE47932PRJNA208378

REPOSITORIES: GEO, ArrayExpress

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Publications

Epigenetic reprogramming modulates malignant properties of human liver cancer.

Raggi Chiara C   Factor Valentina M VM   Seo Daekwan D   Holczbauer Agnes A   Gillen Matthew C MC   Marquardt Jens U JU   Andersen Jesper B JB   Durkin Marian M   Thorgeirsson Snorri S SS  

Hepatology (Baltimore, Md.) 20140501 6


Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. Here we addressed the impact of epigenetic alterations and cellular context on functional and transcriptional reprogramming of hepatocellular carcinoma (HCC) cells. Our strategy employed a 3-day treatment of established and primary human HCC-derived cell lines grown as a monolayer at various cell densities with the DNMT1 inhibitor zebularine (ZEB) followed by a 3D culture to identify cells endo  ...[more]

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