Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 54, Issue 1, Pages 77-86Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2018.4625
Keywords
HOTAIR; gastric cancer; histone modification; epithelial-to-mesenchymal transition; molecular biomarker
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Funding
- China National Natural Scientific Found [81372703, 81172356]
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HOX transcript antisense intergenic RNA (HOTAIR), a well-known long non-coding RNA, plays an important role in the regulation of epithelial-to-mesenchymal transition (EMT). In this study, we propose a novel mechanism through which HOTAIR promotes EMT by switching histone H3 lysine 27 acetylation to methylation at the E-cadherin promoter, which induces the transcriptional inhibition of E-cadherin. HOTAIR recruits polycomb repressive complex 2 (PRC2) to catalyze H3K27me3; however, whether HOTAIR is associated with the acetylation of histone H3 lysine 27, a marker of transcriptional activation, and the mechanisms through which HOTAIR triggers the metastasis of gastric cancer (GC) by epigenetic regulation remain largely unknown. In this study, HOTAIR knockdown significantly reversed EMT by increasing the expression of E-cadherin in GC cells. Additionally, the loss of PRC2 activity induced by HOTAIR knockdown resulted in a global decrease in H3K27 methylation and an increase in H3K27 acetylation. Furthermore, HOTAIR recruits PRC2 (which consists of H3K27 methyltransferase EZH2, SUZ12 and EED), which may inhibit the reaction between the acetyltransferase CBP and H3K27 acetylation. On the whole, the findings of this study suggested that the HOTAIR-mediated acetylation to methylation switch was associated with the transcriptional inhibition of E-cadherin. HOTAIR can promote the development of GC through the epigenetic regulation of E-cadherin, switching the state of the E-cadherin promoter from the transcriptionally active to the transcriptionally repressive state.
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