Upregulation of the long noncoding RNA FOXD2-AS1 promotes carcinogenesis by epigenetically silencing EphB3 through EZH2 and LSD1, and predicts poor prognosis in gastric cancer

作者：Xu, Tong-peng^*; Wang, Wen-yu; Ma, Pei; Shuai, You; Zhao, Kun; Wang, Yan-fen; Li, Wei; Xia, Rui; Chen, Wen-ming; Zhang, Er-bao; Shu, Yong-qian^*

来源：Oncogene, 2018, 37(36): 5020-5036.

DOI：10.1038/s41388-018-0308-y

• COLORECTAL-CANCER
• PROSTATE-CANCER
• CELL-PROLIFERATION
• TUMOR-SUPPRESSOR
• EXPRESSION
• GENE
• INVASIVENESS
• CARCINOMA
• ENHANCER
• GROWTH

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.

• 出版日期2018-9-6
• 单位南京市胸科医院; 扬州大学; 南京医科大学