Abstract

Previous studies determined that circular RNA FOXO3 (circ_FOXO3) plays a critical role in tumorigenesis. The definite molecular mechanism of cir_FOXO3 in endometrial carcinoma (EC), nevertheless, had not been fully explored. Circ_FOXO3 expression was determined using quantitative real-time polymerase chain reaction in human EC tissues and cell lines, whereas small interfering RNAs were used to specifically silence circ_FOXO3 expression in cultured EC cells. The cell counting kit-8 assay was employed to determine the effect of ectopic circ_FOXO3 expression on cell viability. Cell proliferation and apoptosis were evaluated by flow cytometry. Further, migration and invasion of EC cells were characterized using the Transwell assay. The interaction between microRNA (miR)-29a-3p and circ_FOXO3/histone deacetylase 4 (HDAC4) was validated using dual luciferase reporter assay. Additionally, qRT-PCR and WB were employed to determine HDAC4 levels. We found that circ_FOXO3 was highly expressed in EC cells and tissues. Moreover, suppressing circ_FOXO3 expression abrogated EC by regulating cell proliferation, apoptosis, migration, and invasion. Furthermore, circ_FOXO3 could act as a sponge for miR-29a-3p, and inhibition of miR-29a-3p expression reversed the effects of circ_FOXO3 suppression on EC progression. Overexpression of miR-29a-3p inhibited EC cell growth, migration, and invasion through the regulation of HDAC4, as it is a target of miR-29a-3p. In conclusion, circ_FOXO3 promotes EC progression by sponging miR-29a-3p and upregulating HDAC4, making it a promising therapeutic target in EC.