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-AS1 in gastric cancer (GC) progression and related biological mechanisms remain undefined. A comprehensive analysis identified that FOXD2-AS1 enrichment 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-AS1 expression. Loss of FOXD2-AS1 function inhibited cell growth via inhibiting the cell cycle in GC, whereas upregulation of FOXD2-AS1 expression 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-AS1 and mediators of FOXD2-AS1 function. Mechanically, FOXD2-AS1 promoted GC tumorigenesis partly through EZH2 and LSD1 mediated EphB3 downregulation. The present results revealed that FOXD2-AS1 acted 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.

中文翻译：

---

长非编码RNA FOXD2-AS1的上调通过EZH2和LSD1通过表观遗传沉默EphB3促进癌变，并预测胃癌的预后不良。

越来越多的数据表明，长的非编码RNA（lncRNA）在生物过程中起着重要的调节剂作用，并且在多种肿瘤中失调。FOXD2-AS1在胃癌（GC）进展中的功能和相关的生物学机制仍然不确定。全面的分析表明，FOXD2-AS1的富集在GC中显着上调，并且与大的肿瘤大小，较晚的病理分期和不良的预后呈正相关。GEO数据集中的基因集富集分析（GSEA）发现，在FOXD2-AS1高表达的患者中，细胞周期和DNA复制相关基因富集。FOXD2-AS1功能的丧失通过抑制GC中的细胞周期来抑制细胞生长，而FOXD2-AS1表达的上调促进了癌症的进展。发现zeste同源2（EZH2）和赖氨酸（K）特异性脱甲基酶1A（LSD1）蛋白的增强子充当FOXD2-AS1的结合伴侣和FOXD2-AS1功能的介体。在机械上，FOXD2-AS1部分通过EZH2和LSD1介导的EphB3下调促进了GC的肿瘤发生。目前的结果表明，FOXD2-AS1通过与EZH2和LSD1直接相互作用而部分抑制EphB3，从而在GC中起肿瘤诱导剂的作用，并可能被证明是潜在的癌变生物标志物。