Identification of Metastasis‐Associated circRNA‐miRNA‐mRNA Network Reveals Novel Biomarkers and Therapy Strategies for Esophageal Cancer

ABSTRACT circRNAs play pivotal roles in cancer initiation and progression. To explore the metastasis‐related circRNA‐miRNA‐mRNA network in ESCC for novel biomarkers and therapeutic targets, differentially expressed circRNAs, miRNAs, and mRNAs were obtained from GEO datasets. A metastasis‐associated circRNA‐miRNA‐mRNA ceRNA network in ESCC was constructed using Cytoscape software. The STRING database and Cytoscape were utilized for protein–protein interaction (PPI) interaction generation. The GEPIA2 database was used to obtain the expression of downstream targets and their prognostic value. The GO and KEGG enrichment analyzes were performed using the DAVID database. A dual‐luciferase reporter assay was utilized to validate the target interaction among hsa_circ_0007551, miR‐493‐5p, and CXCL8/BMP2. Six metastasis‐related DEcircRNAs overlapped from the GSE131969 and GSE150476 datasets. The ceRNA network was constructed containing six circRNAs, 15 miRNAs, and 86 mRNAs. In the ceRNA network, CXCL8 and BMP2, which were significantly associated with overall survival in ESCC patients, were chosen for further subnetwork construction. Then, a metastatic and survival‐related ceRNA network containing hsa_circ_0007551, miR‐493‐5p, and two DEGs (CXCL8 and BMP2) was identified. hsa_circ_0007551 was upregulated in ESCC tissues and cells. In conclusion, this study identified novel circRNA‐mediated ceRNA networks in ESCC metastasis, highlighting hsa_circ_0007551 and the CXCL8/BMP2 axis as potential biomarkers and therapeutic targets.