Circ_0005615 promotes cervical cancer cell growth and metastasis by modulating the miR‐138‐5p/KDM2A axis

Abstract

AbstractCervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR‐138‐5p, and lysine demethylase 2A (KDM2A) were measured using qRT‐PCR or western blot. Cell proliferation was assessed by Cell Counting Kit‐8, 5‐ethynyl‐2′‐deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase‐Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation‐related and apoptosis‐related markers was detected by western blot. The binding relationships among circ_0005615, miR‐138‐5p, and KDM2A were verified by dual‐luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR‐138‐5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR‐138‐5p, and miR‐138‐5p could target KDM2A. miR‐138‐5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR‐138‐5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR‐138‐5p/KDM2A pathway.