Circular RNA Circ_0003221 Promotes Cervical Cancer Progression by Regulating miR-758-3p/CPEB4 Axis

BACKGROUND: Circular RNAs (circRNAs) play crucial roles in the development and progression of various cancers, including cervical cancer. However, the role and regulatory mechanism of circ_0003221 in cervical cancer are still unclear. METHODS: The expression of circ_0003221, microRNA-758-3p (miR-758-3p), cytoplasmic polyadenylation element-binding protein 4 (CPEB4) was detected by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), colony formation, and 5-Ethynyl-2ʹ-deoxyuridine (Edu) assays were utilized to determine cell proliferation. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected by transwell assay. All protein levels were detected by Western blot assay. The interaction between miR-758-3p and circ_0003221 or CPEB4 was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice xenograft model of cervical cancer was established to verify the function of circ_0003221 in vivo. RESULTS: Circ_0003221 was upregulated in cervical cancer tissues and cells. Knockdown of circ_0003221 suppressed cell proliferation, migration, invasion, and EMT and induced cell cycle arrest in cervical cancer cells. MiR-758-3p was a direct target of circ_0003221, and miR-758-3p inhibition reversed the effects of circ_0003221 knockdown in cervical cancer cells. Moreover, CPEB4 was identified as a direct target of miR-758-3p, and miR-758-3p exerted its anti-cancer role by targeting CPEB4. Furthermore, circ_0003221 acted as a sponge of miR-758-3p to upregulate CPEB4 expression. In addition, circ_0003221 silence also suppressed tumor growth and EMT in vivo. CONCLUSION: Circ_0003221 knockdown inhibited cervical cancer progression via modulating miR-758-3p/CPEB4 axis, which might suggest a new insight into the pathogenesis of cervical cancer.