长链非编码 RNA AFAP1-AS1 通过 miR-155-5p/FGF7 轴促进胃癌细胞增殖和转移，并预测不良预后。

Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer.

机构信息

Department of Emergency Medicine, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Department of Gastroenterology, The Second Provincial People's Hospital of Gansu, Lanzhou, Gansu, China.

出版信息

Dis Markers. 2020 Jan 19;2020:8140989. doi: 10.1155/2020/8140989. eCollection 2020.

BACKGROUND

Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) plays an important role in the development and progression of several human cancers. However, its biological function in gastric cancer (GC) progression is still unknown.

METHODS

We used qRT-PCR to detect the relative expression of AFAP1-AS1 in GC tissues and cell lines. The loss-of-function assays were conducted to detect the effect of AFAP1-AS1 on GC development. Bioinformatics analysis, luciferase reporter gene analysis, and RIP analysis were used to identify and validate target genes of AFAP1-AS1. Finally, rescue tests were performed to confirm the influence of the AFAP1-AS1-miR-155-5p-FGF7 axis on GC development.

RESULTS

AFAP1-AS1 was upregulated in GC tissues and cell lines and was closely correlated with poor prognosis of GC patients. AFAP1-AS1 knockdown inhibited proliferation, migration, and invasion of GC cells, indicating that AFAP1-AS1 acts as an oncogene in GC. Bioinformatics analysis, dual-luciferase reporter gene detection, and RIP assays validated that AFAP1-AS1 directly interacts to miR-155-5p and could positively affect cell proliferation, migration, and invasion by regulation of the expression of miR-155-5p and FGF7. Further rescue assays revealed that AFAP1-AS1 promotes cell proliferation and metastasis through the miR-155-5p/FGF7 axis in GC.

CONCLUSIONS

AFAP1-AS1 might be an oncogenic lncRNA that promoted GC progression by acting as a competing endogenous RNA (ceRNA) that regulates the expression of FGF7 through sponging miR-155-5p, suggesting that AFAP1-AS1 may be a novel potential therapeutic target for GC.

背景

肌动蛋白丝相关蛋白 1 反义 RNA 1（AFAP1-AS1）在几种人类癌症的发生和发展中发挥着重要作用。然而，其在胃癌（GC）进展中的生物学功能尚不清楚。

方法

我们使用 qRT-PCR 检测 GC 组织和细胞系中 AFAP1-AS1 的相对表达。通过功能丧失实验检测 AFAP1-AS1 对 GC 发生发展的影响。生物信息学分析、荧光素酶报告基因分析和 RIP 分析用于鉴定和验证 AFAP1-AS1 的靶基因。最后，进行挽救实验以确认 AFAP1-AS1-miR-155-5p-FGF7 轴对 GC 发生发展的影响。

结果

AFAP1-AS1 在 GC 组织和细胞系中上调，与 GC 患者的不良预后密切相关。AFAP1-AS1 敲低抑制 GC 细胞的增殖、迁移和侵袭，表明 AFAP1-AS1 在 GC 中发挥癌基因作用。生物信息学分析、双荧光素酶报告基因检测和 RIP 实验验证了 AFAP1-AS1 与 miR-155-5p 直接相互作用，并通过调节 miR-155-5p 和 FGF7 的表达，可正向影响细胞增殖、迁移和侵袭。进一步的挽救实验表明，AFAP1-AS1 通过 miR-155-5p/FGF7 轴在 GC 中促进细胞增殖和转移。