The CircZEB1/miR-337-3p/ Axis Mediates Angiogenesis and Metastasis Via O-GlcNAcylation and Up-regulating in Breast Cancer

Background: A growing corpus of research has revealed that circular RNAs (circRNAs) have become increasingly important for the growth of malignancies in recent years. CircRNAs as ideal candidates for breast cancer (BC) therapeutic targets is still absent.

Methods: In our study, the dysregulated circRNAs in BC progression were explored, we analysed the BC's circRNA expression profiles using publicly available datasets (GSE101124 and GSE101122). The expression of circZEB1 in BC and cell lines was investigated by qPCR. RNase and actinomycin D were used to examine the features of circZEB1. The function of circZEB1 was subsequently investigated through the utilisation of colony formation, tube formation, transwell assays, and xenograft animal models.RNA immunoprecipitation (RIP), luciferase reporter assays, immunoprecipitation (co-IP) test in conjunction with LC-MS, and ChIP-seq assay to investigate the molecular mechanism underlying the biological activity of circZEB1 in BC.

Results: Among the circRNAs, we were particularly interested in hsa_circ_0000228, which is spliced from the oncogene . In BC cell lines, CircZEB1 expression was upregulated. CircZEB1 knockdown prevented BC cells from migrating and invading, as well as HUVECs from forming tubes and developing. By sponging miR-337-3p, functional testing revealed that circZEB1 promoted O-GlcNAcylation, increased , and expression. Moreover, circZEB1 overexpression is reversible, in contrast to knockdown, which mostly results in the downregulation of multiple oncogenes.

Conclusion: Our study indicate that circZEB1 had oncogenic function in BC by focusing on circZEB1/miR-337-3p/ and . It might be inferred that circZEB1 could be a promising new target for BC treatment.