Background
Cervical cancer (CC) ranks fourth in terms of incidence and fourth in mortality overall in women worldwide. Circular RNAs (circRNAs) have been shown to be involved in the development of CC. However, the function of circRNA cyclin dependent kinase 17 (circCDK17, hsa_circ_0002762) in CC pathogenesis has not been studied.
Conclusion
Our study demonstrates that circCDK17 regulates the expression of ASF1B by miR-122-5p competition and thus promotes the development of CC, providing a novel targeted therapy for CC.
Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of related genes. MTT, thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays were designed to analyze cell proliferation, cell cycle progression, migration and invasion, respectively. Western blot was utilized to examine the protein levels of Cyclin D1, E-cadherin and Vimentin. The relationship between miR-122-5p and circCDK17 or ASF1B was verified by dual-luciferase reporter assay. The xenograft model was established to study the role of circCDK17 in vivo.
Results
CircCDK17 and anti-silencing function 1B histone chaperone (ASF1B) were highly expressed in CC tissues and cells. Silencing circCDK17 reduced the proliferation, migration and invasion of CC cells. MiR-122-5p was a target of circCDK17. Silencing circCDK17 inhibited the malignant behaviors of CC cells by releasing miR-122-5p. Moreover, ASF1B was a target of miR-122-5p. Overexpression of ASF1B partially restored the inhibitory effects of circCDK17 silencing on cell proliferation, migration and invasion. Animal experiments confirmed the anti-tumor effect of circCDK17 knockdown in vivo.