HERES, a lncRNA that regulates canonical and noncanonical Wnt signaling pathways via interaction with EZH2open access
- Authors
- You, Bo-Hyun; Yoon, Jung-Ho; Kang, Hoin; Lee, Eun Kyung; Lee, Sang Kil; Nam, Jin-Wu
- Issue Date
- Dec-2019
- Publisher
- NATL ACAD SCIENCES
- Keywords
- epigenetic regulation; long noncoding RNA; Wnt signaling pathway; esophageal squamous cell carcinoma
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.116, no.49, pp.24620 - 24629
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 116
- Number
- 49
- Start Page
- 24620
- End Page
- 24629
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/11633
- DOI
- 10.1073/pnas.1912126116
- ISSN
- 0027-8424
- 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.
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