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Review
. 2017 Jun 24;9(7):72.
doi: 10.3390/cancers9070072.

Epigenetic Regulation of the Epithelial to Mesenchymal Transition in Lung Cancer

Joëlle Roche  1 , Robert M Gemmill  2 , Harry A Drabkin  3
Affiliations
Review

Epigenetic Regulation of the Epithelial to Mesenchymal Transition in Lung Cancer

Joëlle Roche et al. Cancers (Basel). .

Abstract

Lung cancer is the leading cause of cancer deaths worldwide. It is an aggressive and devastating cancer because of metastasis triggered by enhanced migration and invasion, and resistance to cytotoxic chemotherapy. The epithelial to mesenchymal transition (EMT) is a fundamental developmental process that is reactivated in wound healing and a variety of diseases including cancer where it promotes migration/invasion and metastasis, resistance to treatment, and generation and maintenance of cancer stem cells. The induction of EMT is associated with reprogramming of the epigenome. This review focuses on major mechanisms of epigenetic regulation mainly in lung cancer with recent data on EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit ), the catalytic subunit of the PRC2 (Polycomb Group PcG), that behaves as an oncogene in lung cancer associated with gene repression, non-coding RNAs and the epitranscriptome.

Keywords: EMT; EZH2; Epigenetics; Epitranscriptomics; NSCLC; SCLC; chromatin modifications; non-coding RNAs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
EMT (Epithelial to Mesenchymal transition ) and epigenetic modifications. EMT is induced by different pathways that involve different transcription factors necessary to repress epithelial genes and to activate mesenchymal genes.
Figure 2
Figure 2
Epigenetic modifications during EMT. Nucleosomes are represented with DNA in red, wrapped around the histone core (2 copies of each histone H2A, H2B, H3 and H4) with the presence of histone H1 in more compact chromatin. Repression of epithelial genes (red cross) is shown with corresponding epigenetic modifications on their promoters: more compact chromatin, decreased H3K9/14/27ac and gain of H3K9me3 and H3K27me3, associated to DNA methylation (red lollipop). Of note, only major modifications for histone H3 are presented. LOCKS (long-range chromatin domains) epigenetic marks during EMT: Global reduction in the heterochromatin mark H3K9me2, increase in the euchromatin mark H3K4me3, and increase in the transcriptional mark H3K36me3. Non-coding RNAs (ncRNAs) expressions are also modified during EMT for miRNAs (loss of miR-200c and miR-149) and lncRNAs (increased HOTAIR and decreased SPRYA-IT1 in lung cancer).
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