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Increase of POU3F3 Promote DNA Methylation in Esophageal Squamous Cell Carcinoma Cells

Author: Zhang Qing
by Zhang Qing
Posted: May 31, 2014
Esophageal squamous cell carcinoma (ESCC) is the ninth most common human cancer in the world and the second most common cancer in China. Long intervening ncRNAs (lincRNAs) were described as RNA molecules longer than 200 nucleotides. POU3F3 has been proven to be involved in the regulation of Delta1 and Sox 2 expression, which are important gene in the neurogenic differentiation of stem cell.

In RNA immunoprecipitation assays, linc-POU3F3 associated with the EZH2 mRNA. Overexpression of Afatinib linc-POU3F3 in cell lines increased their proliferation and ability to form colonies, and reduced expression of POU3F3 mRNA, whereas knockdown of linc-POU3F3 increased levels of POU3F3 mRNA. CpG islands in POU3F3 were hypermethylated in cell lines that overexpressed linc-POU3F3; methylation at these sites was reduced by knockdown of linc-POU3F3. Pharmacologic inhibition of EZH2 increased levels of POU3F3 mRNA and significantly reduced binding of DNMT1, DNMT3A, and DNMT3B to POU3F3. ESCC cells with knockdown of linc-POU3F3 formed screening compounds xenograft tumors more slowly in mice than control

This study is the largest analysis in two-stage clinical ESCC samples for the identification of 13 previously reported sequence and position conserved lincRNAs, and the results show that linc-POU3F3 is overexpressed in ESCC tumor tissues and that linc-POU3F3 promotes cell viability and proliferation in ESCC cells.

Over the past 10 years, many plant-derived compounds were identi?ed for their anti-cancer properties with an emerging?eld regarding the modulation of epigenetic events. Research in the?eld of epigenetic drugs leads to the identi?cation of four molecules that gained FDA approval.

Epigenetic mechanisms namely DNA methylation, histone modi?cations, and regulatory RNA-mediated gene silencing (non-coding RNA) cooperate to sculpt chromatin structure and tune gene expression. In human, DNA methylation corresponds to the addition of a methyl group to cytosine within CpG di nucleotides to form 5-methylcytosine. This reaction is catalyzed by the DNA methyltransferase (DNMT) family. Under normal conditions, these regions are largely unmethylated for most genes, whereas in cancer cells, CpG islands in tumor suppressor genes (TSGs) are frequently hypermethylated and associated to transcriptional gene silencing and inactivation.

Acetylation and methylation of lysine-rich histone tails are two major post-translational modi?cations involved in the regulation of chromatin structure and gene expression. Acetylation is regulated by the balanced enzymatic activities of members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) families.

There is demand to consider the long-term and eventually trans-generational effects of sustained preventive interventions. There is the necessity to identify biomarkers to monitor the ef?ciency of preventive interventions and eventually to predict the need of such interventions, which is going towards a personalized medical approach.

About the Author

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.

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Author: Zhang Qing

Zhang Qing

Member since: Oct 29, 2013
Published articles: 172

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