Upregulation of the long noncoding RNA FOXD2-AS1promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer

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.