期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 49, 页码 24620-24629出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1912126116
关键词
epigenetic regulation; long noncoding RNA; Wnt signaling pathway; esophageal squamous cell carcinoma
资金
- Korean Health Technology R&D Project, Ministry of Health and Welfare [HI15C3224]
- Bio and Medical Technology Development Program
- Basic Science Research Program through the National Research Foundation (NRF)
- Ministry of Science and Information and Communication Technologies (ICT) [2017M3A9G8084539, 2017R1A2B4006316, 2018R1A2B2003782]
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.
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