Oncotarget

Research Papers:

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 _ and Yong Sun Lee

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2014; 5:3472-3481. https://doi.org/10.18632/oncotarget.1927

Metrics: PDF 1749 views  |   HTML 2002 views  |   ?  


Abstract

Hyun-Sung Lee1,2, Kwanbok Lee3, Hee-Jin Jang1, Geon Kook Lee2, Jong-Lyul Park4,5, Seon-Young Kim4,5, Sang-Bae Kim1, Betty H. Johnson3, Jae Ill Zo6, Ju-Seog Lee1,7, Yong Sun Lee3

1 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2 Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, 410-769, Korea

3 Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX77555-1072, USA

4 Medical Genomics Research Center, KRIBB, Daejeon, 305-806, Korea

5 Department of Functional Genomics, University of Science and Technology, Daejeon, 305-806, Korea

6 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

7 Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.

Correspondence:

Yong Sun Lee, email:

Ju-Seog Lee, email:

Keywords: nc886, ESCC, CpG DNA methylation, tumor suppressor

Received: April 18, 2014 Accepted: April 25, 2014 Published: April 27, 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 1927