hsa_circ_0068631 promotes breast cancer progression through c-Myc by binding to EIF4A3

Xuehui Wang; Minghui Chen; Lin Fang

doi:10.1016/j.omtn.2021.07.003

hsa_circ_0068631 promotes breast cancer progression through c-Myc by binding to EIF4A3

Mol Ther Nucleic Acids. 2021 Jul 16:26:122-134. doi: 10.1016/j.omtn.2021.07.003. eCollection 2021 Dec 3.

Authors

Xuehui Wang^{1

2}, Minghui Chen¹, Lin Fang^{1

2}

Affiliations

¹ Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
² Clinical Medical College of Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing 211166, China.

Abstract

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 hsa_circ_0068631, a circRNA generated from the transferrin receptor (TFRC), is upregulated in BC tissues and cell lines. Knockdown of hsa_circ_0068631 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 hsa_circ_0068631 and c-Myc mRNA. Additionally, the expression of hsa_circ_0068631 was positively correlated with c-Myc, and the upregulation of hsa_circ_0068631 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 hsa_circ_0068631 and EIF4A3. Furthermore, hsa_circ_0068631 could recruit EIF4A3 to increase c-Myc mRNA stability. Rescue assays manifesting depletion of c-Myc rescued the promotive effect of hsa_circ_0068631 overexpression on biological activities in BC. In conclusion, to our knowledge, this study is the first to unveil the role of hsa_circ_0068631 and the hsa_circ_0068631/EIF4A3/c-Myc axis in BC, providing a new target for BC treatment.

Keywords: EIF4A3; RBP; breast cancer; c-Myc; hsa_circ_0068631.