Circ_0007624 suppresses the development of esophageal squamous cell carcinoma via targeting miR-224-5p/CPEB3 to inactivate the EGFR/PI3K/AKT signaling

Abstract

Circular RNAs (circRNAs) have been confirmed to be involved in the regulation of esophageal squamous cell carcinoma (ESCC) progression. According to GEO datasets (GSE112496 and GSE150476), we identified that circ_0007624 was abnormally down-regulated in ESCC. However, there is still no reports regarding the function and mechanism of circ_0007624 in ESCC development. Here, we found that circ_0007624 was significantly underexpressed in ESCC tissues, and low expression of circ_0007624 was indicative of a poor prognosis. Overexpressing circ_0007624 or silencing miR-224-5p suppressed cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Also, circ_0007624 up-regulation slowed ESCC tumor growth in vivo. Mechanistically, circ_0007624 could serve as a competing endogenous RNA (ceRNA) by sponging miR-224-5p to antagonize its inhibitory effect on the target cytoplasmic polyadenylation element binding protein 3 (CPEB3). Rescue experiments showed that the anti-cancer properity role of circ_0007624 in ESCC is partly reversed by the restoration of miR-224-5p or down-regulation of CPEB3. Furthermore, EGFR/PI3K/AKT pathway was involved in the regulation of circ_0007624/miR-224-5p/CPEB3 axis in ESCC. Together, our findings demonstrate for the first time that circ_0007624/miR-224-5p/CPEB3 suppresses ESCC progression by inactivating EGFR/PI3K/AKT signaling, providing a basis for developing circ_0007624-targeted therapies for ESCC patients.