Department of Gastrointestinal Surgery, Qingdao Central Hospital, Qingdao, China.
Eur Rev Med Pharmacol Sci. 2019 Oct;23(19):8371-8376. doi: 10.26355/eurrev_201910_19148.
To clarify the role of lncRNA FOX4-AS1 in the progression of gastric cancer (GC) via interacting with EZH2/LSD1.
Relative level of FOXP4-AS1 in GC tissues and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The potential influences of FOXP4-AS1 on cellular behaviors of GC cells were evaluated via a series of functional experiments. Bioinformatics prediction, RNA immunoprecipitation (RIP) assay, and Western blot were conducted to verify the potential of EZH2/LSD1 as a target of FOXP4-AS1.
FOXP4-AS1 was upregulated in GC tissues relative to controls. Its level was higher in GC patients with stage III-IV than those with stage I-II. The survival rate was lower in GC patients presenting the high expression of FOXP4-AS1 compared with those presenting low expression. Transfection of sh-FOXP4-AS1 1# or sh-FOXP4-AS1 2# attenuated proliferative, migratory, and invasive abilities of AGS and BGC7901 cells. FOXP4-AS1 could bind to LSD1 and EZH2, and positively regulated their expression levels. Transfection of sh-LSD1 or sh-EZH2 reduced the proliferative ability of GC cells.
FOXP4-AS1 binds to EZH2/LSD1 to form a carcinogenic complex, thus accelerating GC cells to proliferate, migrate and invade.
通过与 EZH2/LSD1 相互作用，阐明 lncRNA FOX4-AS1 在胃癌（GC）进展中的作用。
通过实时定量聚合酶链反应（qRT-PCR）测定 GC 组织和相邻正常组织中 FOXP4-AS1 的相对水平。通过一系列功能实验评估 FOXP4-AS1 对 GC 细胞细胞行为的潜在影响。通过生物信息学预测、RNA 免疫沉淀（RIP）测定和 Western blot 验证 EZH2/LSD1 作为 FOXP4-AS1 的潜在靶点。
FOXP4-AS1 在 GC 组织中相对于对照上调。在 III-IV 期 GC 患者中，其水平高于 I-II 期患者。与 FOXP4-AS1 低表达的 GC 患者相比，FOXP4-AS1 高表达的 GC 患者的生存率较低。转染 sh-FOXP4-AS1 1# 或 sh-FOXP4-AS1 2# 可减弱 AGS 和 BGC7901 细胞的增殖、迁移和侵袭能力。FOXP4-AS1 可与 LSD1 和 EZH2 结合，并正向调节其表达水平。转染 sh-LSD1 或 sh-EZH2 可降低 GC 细胞的增殖能力。
FOXP4-AS1 与 EZH2/LSD1 结合形成致癌复合物，从而加速 GC 细胞增殖、迁移和侵袭。
