lncRNA GCAWKR Promotes Gastric Cancer Development by Scaffolding the Chromatin Modification Factors WDR5 and KAT2A
Long noncoding RNAs (lncRNAs) have been demonstrated to play a role in carcinogenesis, but their mechanisms of function remain elusive. We explored the mechanisms of the oncogenic role of GCAWKR in gastric cancer (GC) using human tissues and cell lines. The in situ hybridization analysis was utilize...
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Published in | Molecular therapy Vol. 26; no. 11; pp. 2658 - 2668 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
07.11.2018
Elsevier Limited American Society of Gene & Cell Therapy |
Subjects | |
Online Access | Get full text |
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Summary: | Long noncoding RNAs (lncRNAs) have been demonstrated to play a role in carcinogenesis, but their mechanisms of function remain elusive. We explored the mechanisms of the oncogenic role of GCAWKR in gastric cancer (GC) using human tissues and cell lines. The in situ hybridization analysis was utilized to determine GCAWKR levels in samples from 42 GC patients and real-time qPCR in tissues from 123 patients. The GCAWKR levels were modulated in GC cell lines, and relevant biological and molecular analyses were performed. Levels of the GCAWKR were upregulated in GC tissues compared with normal tissues and associated with tumor size, lymph node metastasis, TNM stage, and patient outcomes. GCAWKR affected cell proliferation and cell invasion in multiple GC models. Mechanistically, GCAWKR bound WDR5 and KAT2A and acted as a molecular scaffold of WDR5/KAT2A complexes, modulating the affinity for WDR5/KAT2A complexes in the target gene’s promoter region. Thus, our data defined a mechanism of lncRNA-mediated carcinogenesis in GC, suggesting new therapeutic targets in GC.
Ma et al. show that lncRNA-GCAWKR regulates gastric cancer development. GCAWKR was upregulated in GC tissues compared with normal tissues and was associated with patient outcomes. Mechanistically, GCAWKR acted as a molecular scaffold for WDR5/KAT2A complexes, thereby modulating the affinity for WDR5/KAT2A complexes in the target gene’s promoter region. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. |
ISSN: | 1525-0016 1525-0024 |
DOI: | 10.1016/j.ymthe.2018.09.002 |