Aim: To explore the role and potential mechanism of circSND1 in cervical cancer (CC).
Main Methods: qRT-PCR was used to determine the expression of circSND1 in tumor necrosis factor-α (TNF-α)-treated HeLa cells. CircSND1 overexpression and knockdown were performed to indicate the functional role of circSND1 in vitro and in vivo. Luciferase assay was used to analyze promoter activity. The expression and regulation of circSND1, miR-125a-3p and FUT6 were evaluated using EGFP fluorescent reporter assay and rescue experiments. Immunofluorescence and Western blot assays were used to analyze the activation of nuclear factor-κB (NF-κB).
Results: In HeLa cells, TNF-α up-regulated the expression of circSND1 by activating the NF-κB signaling pathway. Overexpression of circSND1 significantly increased the migration and invasion and the epithelial–mesenchymal transition (EMT) process of CC cells, and promoted tumor metastasis in xenograft nude mouse model, whereas down-regulation of circSND1 exerted opposite effects. Furthermore, circSND1 enhanced the expression of FUT6 via sponging miR-125a-3p, and FUT6 activated NF-κB signaling pathway.
Conclusion: We found that circSND1 promoted the expression of FUT6 and the malignant behavior of cervical cancer through the ceRNA mechanism, and there was a TNF-α/NF-κB/circSND1/miR-125a-3p/FUT6/NF-κB positive feedback pathway between them, which suggests that circSND1 can be a promising prognostic marker and therapeutical target for cervical cancer.
Keywords: circSND1, miR-125a-3p, FUT6, NF-κB, ceRNA, cervical cancer