Abstract
A-to-I RNA editing is a pervasive mechanism in the human genome that affects the regulation of gene expression and is closely associated with the pathogenesis of numerous diseases. This study elucidates the regulatory mechanism of A-to-I edited miR-1304-3p in esophageal squamous cell carcinoma (ESCC). Western blot, immunohistochemistry, and RT-qPCR assays were employed to quantify protein and mRNA expression. Colony formation, Edu, wound healing, and Transwell assays were applied to determine miRNA function. Glycolysis was assessed using glucose uptake and lactate production assay. A dual-luciferase reporter assay confirmed the downstream targets of miRNA, and a xenograft assay demonstrated the efficacy of the miRNA. The A-to-I RNA editing level of miR-1304-3p was observed to increase in KYSE180 and KYSE140 ESCC cells following ADAR1 treatment. Following A-to-I editing, the function of miR-1304-3p in ESCC progression underwent a reversal, shifting from carcinogenic to inhibitory. Wild-type (WT) miR-1304-3p targets IRS1, whereas the edited version targets ROR2. The WT miR-1304-3p, but not the edited version, suppressed the expression and tumor-suppressive effect of IRS1 in ESCC. Conversely, ROR2, a specific downstream target of the edited miR-1304-3p, acted as a tumor promoter in ESCC. Furthermore, A-to-I editing of miR-1304-3p can inhibit glycolysis and inactivate the Wnt5a/ROR2 signaling pathway in ESCC. A-to-I RNA editing alters the function of miR-1304-3p in ESCC by changing its target gene. The edited miR-1304-3p hinders the development of ESCC by inhibiting glycolysis and inactivating the Wnt5a/ROR2 signaling pathway.