Cancer susceptibility 18 positively regulates NUAK Family Kinase 1 expression to promote migration and invasion via sponging of miR-5586-5p in cervical cancer cells.

Abstract

Introduction: Cervical squamous cell carcinoma (CESC) is the most common gynecological malignancy worldwide. Although the cancer susceptibility 18 (CASC18) gene was involved in the regulation of cancer biology, its specific role in CESC is not well characterized.

Methods: CASC18-related axis was predicted by bioinformatic analyses, and the competing endogenous RNA (ceRNA) interaction was further validated using quantitative real-time PCR, western blotting, RNA pulldown, and luciferase reporter assays. Transwell and wound healing assays were performed to verify the effect of CASC18 on SiHa and HeLa cell motility.

Results: We found that CASC18 was upregulated in CESC tissues. Moreover, interference with CASC18 attenuated NUAK1-mediated epithelial-mesenchymal transition (EMT) and thus suppressed cancer cell motility. Furthermore, the effects of CASC18 knockdown on CESC cells were partly rescued by transfection with the miR-5586-5p inhibitor. Additionally, our findings indicated that CASC18 acts as a ceRNA to enhance NUAK1 expression by sponging miR-5586-5p.

Conclusion: Our study showed a novel CASC18/miR-5586-5p/NUAK1 ceRNA axis that could regulate cell invasion and migration by modulating EMT in CESC. These findings suggest that CASC18 may potentially serve as a novel therapeutic target in CESC treatment.