Abstract
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.
Highlights
Gastric cancer (GC) is one of the most common malignancies worldwide [1, 2]
Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) regulated gene expression through functioning as microRNA sponge or competing endogenous RNA and play significant regulatory roles in tumor biology via Disease Markers various mechanisms associating with the aggressive development of cancer, including cell proliferation, differentiation, apoptosis, invasion, metabolism, developmental timing, and immune responses [16,17,18]
To investigate the level of AFAP1-AS1 in human gastric cancer (GC) tissues and GC cell lines, Quantitative real-time PCR (qRT-PCR) was conducted. qRT-PCR results illustrated that AFAP1-AS1 was overexpressed in GC tissues compared with adjacent normal tissues (Figure 1(a)) and was upregulated in GC cell lines (MKN-28, BGC-823, MGC-803, and SGC7901) compared with the gastric mucosal epithelial cell lines GES-1 (Figure 1(b))
Summary
Gastric cancer (GC) is one of the most common malignancies worldwide [1, 2]. diagnosis and treatment strategies have been improved, a large number of newly diagnosed GC cases have occurred over the past decades [3, 4]. Increasing studies have demonstrated that lncRNAs regulated gene expression through functioning as microRNA (miRNA) sponge or competing endogenous RNA (ceRNA) and play significant regulatory roles in tumor biology via Disease Markers various mechanisms associating with the aggressive development of cancer, including cell proliferation, differentiation, apoptosis, invasion, metabolism, developmental timing, and immune responses [16,17,18]. 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. 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
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