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Upregulation of the long noncoding RNA FOXD2-AS1promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer
- Source :
- Oncogene; September 2018, Vol. 37 Issue: 36 p5020-5036, 17p
- Publication Year :
- 2018
-
Abstract
- Accumulating data indicate that long noncoding RNAs (lncRNAs) serve as important modulators in biological processes and are dysregulated in diverse tumors. The function of FOXD2-AS1in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1enrichment was upregulated markedly in GC and positively correlated with a large tumor size, a later pathologic stage, and a poor prognosis. Gene-set enrichment analysis (GSEA) in GEO datasets uncovered that cell cycle and DNA replication associated genes were enriched in patients with high FOXD2-AS1expression. Loss of FOXD2-AS1function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1expression promoted cancer progression. The enhancer of zeste homolog 2 (EZH2) and lysine (K)-specific demethylase 1A (LSD1) proteins were found to serve as binding partners of FOXD2-AS1and mediators of FOXD2-AS1function. Mechanically, FOXD2-AS1promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1acted as a tumor inducer in GC partly through EphB3 inhibition by direct interaction with EZH2 and LSD1, and may prove to be a potential biomarker of carcinogenesis.
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Volume :
- 37
- Issue :
- 36
- Database :
- Supplemental Index
- Journal :
- Oncogene
- Publication Type :
- Periodical
- Accession number :
- ejs50163388
- Full Text :
- https://doi.org/10.1038/s41388-018-0308-y