Circ_0003221 Downregulation Restrains Cervical Cancer Cell Growth, Metastasis and Angiogenesis by Governing the miR-139-3p/S100A14 Pathway

Circular RNA (circRNA) has considerable potency in carcinogenesis, which has aroused much attention. The objective of our study was to disclose the role of circ_0003221 in cervical cancer. Circ_0003221, miR-139-3p, and S100 calcium-binding protein A14 (S100A14) mRNA were quantified by quantitative real-time PCR (qPCR). The proliferation of cancer cells was checked by CCK-8 assay and EdU assay. The migration and invasion of cancer cells were checked by transwell assay. Angiogenesis was determined by tube formation assay. The protein levels of epithelial-mesenchymal transition (EMT)-related markers, angiogenesis-related markers, and S100A14 protein were measured by western blot. The interplays between miR-139-3p and circ_0003221 or S100A14 were ensured by RIP assay and dual-luciferase reporter assay. Further animal study was conducted to verify the role of circ_0003221 in vivo. Circ_0003221 was highly expressed in cancer tissues and cells, and its downregulation suppressed cancer cell proliferation, migration, invasion, and angiogenesis and also delayed tumor growth in vivo. Circ_0003221 bound to miR-139-3p and sequestered miR-139-3p expression. The inhibitory cancer cell biological behaviors by circ_0003221 downregulation were recovered by miR-139-3p suppression. S100A14 was a target gene of miR-139-3p. MiR-139-3p upregulation repressed cancer cell malignant phenotypes by depleting S100A14. Importantly, circ_0003221 positively regulated S100A14 expression by targeting miR-139-3p. Circ_0003221 downregulation restrains cervical cancer cell growth, metastasis, and angiogenesis by governing the miR-139-3p/S100A14 pathway.

Automated summary

The study revealed the impact of circ_0003221 on proliferation, migration, invasion, and angiogenesis of cervical cancer cells, acting through the miR-139-3p/S100A14 pathway.