The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
LncRNA HOXA11-AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1
Abstract
Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer through an analysis of The Cancer Genome Atlas RNA sequencing data and other publicly available microarray data. Here we report the gastric cancer–associated lncRNA HOXA11-AS as a key regulator of gastric cancer development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, and apoptosis. Strikingly, high-throughput sequencing analysis after HOXA11-AS silencing highlighted alterations in cell proliferation and cell–cell adhesion pathways. Mechanistically, EZH2 along with the histone demethylase LSD1 or DNMT1 were recruited by HOXA11-AS, which functioned as a scaffold. HOXA11-AS also functioned as a molecular sponge for miR-1297, antagonizing its ability to repress EZH2 protein translation. In addition, we found that E2F1 was involved in HOXA11-AS activation in gastric cancer cells. Taken together, our findings support a model in which the EZH2/HOXA11-AS/LSD1 complex and HOXA11-AS/miR-1297/EZH2 cross-talk serve as critical effectors in gastric cancer tumorigenesis and progression, suggesting new therapeutic directions in gastric cancer. Cancer Res; 76(21); 6299–310. ©2016 AACR.
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“The lncRNA-mediated assembly of PRC2 and LSD1 coordinates targeting of PRC2 and LSD1 for coupled H3K27 methylation and H3K4 demethylation (48).”
BackgroundSelf-citationThe Polycomb group protein EZH2 directly controls DNA methylation
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Cited by
A novel long noncoding RNA HOXC-AS3 mediates tumorigenesis of gastric cancer by binding to YBX1
Zhang, E., He, X., Zhang, C., Su, J., Lu, X., Si, X., Chen, J., Yin, D., Han, L., & De, W. (2018) · Genome Biology · doi:10.1186/s13059-018-1523-0 · Cited by 282
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Metadata
- Authors
- Sun, M., Nie, F., Wang, Y., Zhang, Z., Hou, J., He, D., Xie, M., Xu, L., De, W., Wang, Z., & Wang, J.
- Venue
- Cancer Research
- Published
- 2016-10-31
- Volume
- 76
- Issue
- 21
- Pages
- 6299-6310
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2521827132
- Cited by
- 469
- References
- 53
- FWCI
- 26.20
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Sun, M., Nie, F., Wang, Y., Zhang, Z., Hou, J., He, D., Xie, M., Xu, L., De, W., Wang, Z., & Wang, J. (2016). LncRNA HOXA11-AS Promotes Proliferation and Invasion of Gastric Cancer by Scaffolding the Chromatin Modification Factors PRC2, LSD1, and DNMT1. Cancer Research. https://doi.org/10.1158/0008-5472.can-16-0356
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