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HERES, a lncRNA that regulates canonical and noncanonical Wnt signaling pathways via interaction with EZH2

Authors
 Bo-Hyun You  ;  Jung-Ho Yoon  ;  Hoin Kang  ;  Eun Kyung Lee  ;  Sang Kil Lee  ;  Jin-Wu Nam 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.116(49) : 24620-24629, 2019 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2019
Keywords
Wnt signaling pathway ; epigenetic regulation ; esophageal squamous cell carcinoma ; long noncoding RNA
Abstract
Wnt signaling through both canonical and noncanonical pathways plays a core role in development. Dysregulation of these pathways often causes cancer development and progression. Although the pathways independently contribute to the core processes, a regulatory molecule that commonly activates both of them has not yet been reported. Here, we describe a long noncoding RNA (lncRNA), HERES, that epigenetically regulates both canonical and noncanonical Wnt signaling pathways in esophageal squamous cell carcinoma (ESCC). For this study, we performed RNA-seq analysis on Korean ESCC patients and validated these results on a larger ESCC cohort to identify lncRNAs commonly dysregulated in ESCCs. Six of the dysregulated lncRNAs were significantly associated with the clinical outcomes of ESCC patients and defined 4 ESCC subclasses with different prognoses. HERES reduction repressed cell proliferation, migration, invasion, and colony formation in ESCC cell lines and tumor growth in xenograft models. HERES appears to be a transacting factor that regulates CACNA2D3, SFRP2, and CXXC4 simultaneously to activate Wnt signaling pathways through an interaction with EZH2 via its G-quadruple structure-like motif. Our results suggest that HERES holds substantial potential as a therapeutic target for ESCC and probably other cancers caused by defects in Wnt signaling pathways.
Files in This Item:
T201905492.pdf Download
DOI
10.1073/pnas.1912126116
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174761
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