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Overexpression of long noncoding RNA LINC01419 in esophageal squamous cell carcinoma and its relation to the sensitivity to 5-fluorouracil by mediating GSTP1 methylation.


ABSTRACT: Background:Genome-wide sequencing investigations have identified numerous long noncoding RNAs (lncRNAs) among mammals, many of which exhibit aberrant expression in cancers, including esophageal squamous cell carcinoma (ESCC). Herein, this study elucidates the role and mechanism by which LINC01419 regulates the DNA methylation of glutathione S-transferase pi 1 (GSTP1) in relation to ESCC progression and the sensitivity of ESCC cells to 5-fluorouracil (5-FU). Methods:LINC01419 and GSTP1 levels were quantified among 38 paired ESCC and adjacent tissue samples collected from patients with ESCC. To ascertain the contributory role of LINC01419 in the progression of ESCC and identify the interaction between LINC01419 and GSTP1 promoter methylation, LINC01419 was overexpressed or silenced, and the DNA methyltransferase inhibitor 5-Aza-CdR was treated. Results:Data from the GEO database (GSE21362) and the Cancer Genome Atlas displayed elevated levels of LINC01419 and downregulated levels of GSTP1 in the ESCC tissues and cells. The silencing of LINC01419 led to decreased proliferation, increased apoptosis, and enhanced sensitivity to 5-FU in ESCC cells. Notably, LINC01419 could bind to the promoter region of the GSTP1 gene, resulting in elevated GSTP1 methylation and reduced GSTP1 levels via the recruitment of DNA methyltransferase among ESCC cells, whereby ESCC progression was stimulated accompanied by reduced ESCC cell sensitivity to 5-FU. GSTP1 demethylation by 5-Aza-CdR was observed to reverse the effects of LINC01419 overexpression in ESCC cells and the response to 5-FU. Conclusion:Highly expressed LINC01419 in ESCC promotes GSTP1 methylation, which ultimately acts to promote the event of ESCC and diminish the sensitivity of ESCC cells to 5-FU, highlighting a novel potential strategy to improve 5-FU-based chemotherapy in ESCC.

SUBMITTER: Chen JL 

PROVIDER: S-EPMC6463338 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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