hsacirc₀068631 promotes breast cancer progression through c-Myc by binding to EIF4A3

Breast cancer (BC) is one of the most common malignancies among women worldwide with a high incidence of recurrence and metastasis. In this study, we demonstrate that hsacirc₀068631, a circRNA generated from the transferrin receptor (TFRC), is upregulated in BC tissues and cell lines. Knockdown of hsacirc₀068631 inhibited the proliferation and migration of BC cells in vitro and in vivo. Mechanistically, an RNA pull-down assay and RNA immunoprecipitation assay revealed that eukaryotic translation initiation factor 4A3 (EIF4A3) could bind to hsacirc₀068631 and c-Myc mRNA. Additionally, the expression of hsacirc₀068631 was positively correlated with c-Myc, and the upregulation of hsacirc₀068631 was a crucial factor for the dysregulation of c-Myc. Through an actinomycin D assay, we confirmed that the mRNA stability of c-Myc was influenced by hsacirc₀068631 and EIF4A3. Furthermore, hsacirc₀068631 could recruit EIF4A3 to increase c-Myc mRNA stability. Rescue assays manifesting depletion of c-Myc rescued the promotive effect of hsacirc₀068631 overexpression on biological activities in BC. In conclusion, to our knowledge, this study is the first to unveil the role of hsacirc₀068631 and the hsacirc₀068631/EIF4A3/c-Myc axis in BC, providing a new target for BC treatment.