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Title 

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

Authors 

H S LeeK LeeH J JangG K LeeJong Lyul ParkSeon-Young KimS B KimB H JohnsonJ I ZoJ S LeeY S Lee

Publisher 

Impact Journals

Issue Date 

2014

Citation 

Oncotarget, vol. 5, no. 11, pp. 3472-3481

Keywords 

CpG DNA methylationESCCnc886Tumor suppressor

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.

ISSN 

1949-2553

Link 

http://dx.doi.org/10.18632/oncotarget.1927

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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