Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis

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Title
Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis
Author(s)
H S Lee; K Lee; H J Jang; G K Lee; Jong Lyul ParkSeon-Young Kim; S B Kim; B H Johnson; J I Zo; J S Lee; Y S Lee
Bibliographic Citation
Oncotarget, vol. 5, no. 11, pp. 3472-3481
Publication Year
2014
Abstract
nc886 (= vtRNA2-1 or pre-miR-886) is a recently discovered noncoding RNA that is a cellular PKR (Protein Kinase RNA-activated) ligand and repressor. nc886 has been suggested to be a tumor suppressor, solely based on its expression pattern and genomic locus. In this report, we have provided sufficient evidence that nc886 is a putative tumor suppressor in esophageal squamous cell carcinoma (ESCC). In 84 paired specimens from ESCC patients, nc886 expression is significantly lower in tumors than their normal adjacent tissues. More importantly, decreased expression of nc886 is significantly associated with shorter recurrence-free survival of the patients. Suppression of nc886 is mediated by CpG hypermethylation of its promoter, as evidenced by its significant negative correlation to nc886 expression in ESCC tumors and by induced expression of nc886 upon demethylation of its promoter. Knockdown of nc886 and consequent PKR activation induce FOS and MYC oncogenes as well as some inflammatory genes including oncogenic NF-κB. When ectopically expressed, nc886 inhibits proliferation of ESCC cells, further demonstrating that nc886 could be a tumor suppressor. All these findings implicate nc886 as a novel, putative tumor suppressor that is epigenetically silenced and regulates the expression of oncogenes in ESCC.
Keyword
CpG DNA methylationESCCnc886Tumor suppressor
ISSN
1949-2553
Publisher
Impact Journals
DOI
http://dx.doi.org/10.18632/oncotarget.1927
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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