Abstract
This study aims to investigate the regulatory impact of hsa_circ_0043,603, a circular RNA, on the progression of esophageal squamous cell carcinoma (ESCC), which ranks as the sixth leading cause of global mortality. We evaluated the expression, origin, and localization of hsa_circ_0043,603 in ESCC tumors using qRT-PCR, bioinformatics, and FISH analysis. Functional studies were conducted by manipulating the hsa_circ_0043,603 expression in Eca109 cells through overexpression and silencing plasmids. Additionally, xenografts derived from circ_0043,603-overexpressing Eca109 cells enabled us to investigate tumor growth, proliferation, and apoptosis. Through Starbase analysis, we identified miR-1178-3p as a target of circ_0043,603, which was validated using RIP and luciferase assays. Furthermore, we predicted arylacetamide deacetylase (AADAC) as a target of miR-1178-3p and examined its expression in ESCC tissues using Western blot. Lastly, we performed AADAC silencing and overexpression in Eca109 cells to study their impact on cellular phenotypic features, apoptosis, and their interaction with miR-1178-3p mimics and inhibitors. The low expression of hsa_circ_0043,603 in ESCC tissue was associated with poor prognosis. Overexpression of hsa_circ_0043,603 inhibited ESCC growth, invasion, migration, and proliferation, while promoting apoptosis in vitro and suppressing tumor growth in vivo. hsa_circ_0043,603 achieved these effects by targeting the oncogenic miR-1178-3p. Furthermore, AADAC was identified as a target of miR-1178-3p, and its reduced expression was confirmed in ESCC tissues. Overexpression of AADAC in Eca109 cells resulted in suppressed cell growth, proliferation, migration, and invasion by regulating miR-1178-3p. hsa_circ_0043,603 acts as a sponge for miR-1178-3p, leading to the regulation of AADAC expression and inhibition of ESCC development. These results suggest the potential of hsa_circ_0043,603 as a therapeutic and diagnostic target for ESCC.