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Effects of NSD2 depletion on gene expression and H3K36me2 in a lung cancer cell line

ABSTRACT: The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. Co-treatment with MEK and BRD4 inhibitors causes co-operative inhibitory responses on cell growth. While these inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition complements their action by affecting the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73696 | GEO | 2017/02/14

SECONDARY ACCESSION(S): PRJNA297680

REPOSITORIES: GEO

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