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

Hyun Sung Lee, Kwanbok Lee, Hee Jin Jang, Geon Kook Lee, Jong Lyul Park, Seon Young Kim, Sang Bae Kim, Betty H. Johnson, Jae Ill Zo, Ju Seog Lee, Yong Sun Lee

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3472-3481
Number of pages10
JournalOncotarget
Volume5
Issue number11
DOIs
StatePublished - 2014

Keywords

  • CpG DNA methylation
  • ESCC
  • Tumor suppressor
  • nc886

ASJC Scopus subject areas

  • Oncology

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    Lee, H. S., Lee, K., Jang, H. J., Lee, G. K., Park, J. L., Kim, S. Y., Kim, S. B., Johnson, B. H., Zo, J. I., Lee, J. S., & Lee, Y. S. (2014). Epigenetic silencing of the non-coding RNA nc886 provokes oncogenes during human esophageal tumorigenesis. Oncotarget, 5(11), 3472-3481. https://doi.org/10.18632/oncotarget.1927