Background: Cervical cancer (CC) is the 4th most common malignancy and cancer-related fatality in women worldwide. Circular RNA is a newly recognized noncoding RNA form. More reports have confirmed their important regulatory functions in diverse physiological and cancer processes. However, the function and mechanisms of circ-HIPK3 in CC remain unknown.
Methods: circ-HIPK3 expression status was verified between 45 paired CC and normal adjacent tissues from 45 CC patients, also the 6 CC cell lines and a normal human cervical epithelial End1/E6E7 cell line by qRT-PCR. Effects of circ-HIPK3 silence on CC cell phenotypes were estimated. Circular RNA interactome was applied to forecast binding site between circ-HIPK3 and miRNAs. Pearson correlation analysis was used to confirm the relationship between genes. Point mutation, RNA pull-down, luciferase assay and rescue experiments were applied for molecular mechanism exploration.
Results: circ-HIPK3 expression was significantly elevated in CC cells and tissues. circ-HIPK3 silence repressed growth and metastasis, while induced apoptosis in CC cells. circ-HIPK3 sponged miRNA-338-3p (miR-338-3p); miR-338-3p to up-regulate hypoxia-inducible factor-1α (HIF-1α) and CC progress. MiR-338-3p silence or HIF-1α over-expression rescued circ-HIPK3 knockdown caused inhibition of CC malignant characteristics.
Conclusion: circ-HIPK3 acts as a competing endogenous RNA of miR-338-3p to promote cell growth and metastasis in CC, via regulating HIF-1α mediated EMT. Therefore, targeting circ-HIPK3/miR-338-3p/HIF-1α axis may be a novel therapeutic strategy for CC.
Keywords: cervical cancer, circ-HIPK3, miR-338-3p, HIF-1α, EMT, metastasis