EIF4A3-induced circZFAND6 promotes breast cancer proliferation and metastasis through the miR-647/FASN axis

Aims: Circular RNAs (circRNAs) are important regulators in breast cancer progression. However, the underlying mechanism of circRNAs functions in breast cancer remain largely unclear.Main methods: To investigate the circRNAs expression pattern in breast cancer, high-throughput circRNA microarray assay was used. The top up-regulated circRNA, circZFAND6, was submitted to further experiments, including cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assay and mouse xenograft assay. To investigate the underlying mechanism of circZFAND6 function in breast cancer progression, luciferase re-porter assay and RNA immunoprecipitation (RIP) assay were conducted.Key findings: We found a novel circRNA, circZFAND6, was up-regulated in breast cancer tissues and cell lines. Inhibition of circZFAND6 reduced proliferation and metastasis of breast cancer. Mechanically, circZFAND6 acted as a competing endogenous RNA (ceRNA) to sponge miR-647 and increase fatty acid synthase (FASN) expression. And eukaryotic translation initiation factor 4A3 (EIF4A3) was found to bind to circZFAND6 pre-mRNA transcript upstream region, leading to the high expression of circZFAND6 in breast cancer. Inhibition of EIF4A3 also suppressed proliferation and metastasis of breast cancer.Significance: EIF4A3-induced circZFAND6 up-regulation promoted proliferation and metastasis of breast cancer through the miR-647/FASN axis. Our results uncovered a possible mechanism underlying breast cancer pro-gression and might provide a breast cancer treatment target.

Automated summary

This study discovered a novel circular RNA, circZFAND6, which was up-regulated in breast cancer tissues and cell lines. Inhibition of circZFAND6 reduced proliferation and metastasis of breast cancer. Mechanistically, circZFAND6 acted as a competing endogenous RNA (ceRNA) to sponge miR-647 and increase fatty acid synthase (FASN) expression. Additionally, EIF4A3 was found to bind to the upstream region of circZFAND6 pre-mRNA transcript, leading to the high expression of circZFAND6 in breast cancer. Inhibition of EIF4A3 also suppressed proliferation and metastasis of breast cancer.