Function of As a Competing Endogenous RNA to Promote Progression in Gastric Cancer by Regulating the Axis

Background: Mounting evidences indicate that circular RNAs (circRNAs) are a novel class of non-coding RNAs and play vital roles in the tumorigenesis and aggressiveness including gastric cancer (GC). Nevertheless, the precise functions and underlying mechanisms of circRNAs in GC remain largely unknown.

Methods: The Gene Expression Omnibus (GEO) data set GSE163416 was analyzed to screen the key circRNAs in GC. was chosen for further study. GC tissues and matched adjacent normal gastric mucosal epithelial tissues were obtained from the Fourth Hospital of Hebei Medical University. The expressions of was detected using quantitative real-time polymerase chain reaction (qRT-PCR). was knocked down to identify its effects on GC cells. Bioinformatics algorithms were analyzed to predict the microRNA (miRNAs) potentially sponged by and its target genes. Fluorescence in situ hybridization (FISH) was conducted to determine the subcellular location of and the predicted miRNA. Then, qRT-PCR, luciferase reporter assay, radioimmunoprecipitation assay, Western blotting, and miRNA rescue experiments were used to confirm the -related regulatory axis in GC. Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell experiments were performed to determine the effect of the hsa_-related regulatory axis on GC cells' malignant behaviors . The xenograft tumor mouse model was established to evaluate the effect of .

Results: exhibited a high expression in GC tissues as compared to corresponding adjacent normal gastric mucosal epithelial tissues and its high expression was positively correlated with TNM stage, lymph node invasion and poor prognosis (P<0.05). Knockdown of suppressed the proliferation, colony formation, migration, and invasion in GC cells (all P<0.05). upregulated high mobility group box 1 () by sponging in GC cells (P<0.05). The - axis promoted malignant behaviors and epithelial-mesenchymal transition (EMT) in GC cells by activating the Wnt/β-catenin pathway (P<0.05). The existence of - axis was confirmed in GC specimens (P<0.05). Consequently, down-regulated inhibited the progression and EMT of GC cells (P<0.05).

Conclusions: For the first time, we demonstrated that axis exerted its tumor-promoting effects in GC, which suggested that could be potentially targeted for GC treatment.