Mechanism study of EIF4A3-induced circ_0022382 regulation of breast cancer cell biology

Abstract

Breast cancer is one of the most common cancers in women and poses a serious threat to women's health. In this paper, we examined the role of circular (circ)RNA in breast cancer, and screened out circ_0022382 for high expression in breast cancer by differential analysis of breast cancer and adjacent tissues in the GEO database. The high expression of circ_0022382 in breast cancer cell lines MDA-MB-231, MCF-7 as well as breast cancer tissues was confirmed by qRT-PCR. The proliferation, migration and apoptosis of MDA-MB-231 and MCF-7 breast cancer cells were significantly increased by transfection of siRNA targeting circ_0022382, and dual luciferase reporter assays showed that circ_0022382 bound to microRNA (miR) let-7a-5p. Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis predicted that the mammalian target of rapamycin (mTOR) and phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathways were the main pathways regulated by let-7a-5p. The addition of let-7a-5p inhibitor reduced the proliferation and migration of breast cancer cells caused by circ_0022382 knockdown by rescuing the expression of p-AKT. Let-7a-5p also directly regulates the expression of cystine transporter solute carrier family 7 member 11 (SLC7A11) proteins, and through examination of glucose in cell supernatants and the addition of cystine inhibitors (dithiothreitol), we found that this process was closely related to disulfidptosis. In addition, eukaryotic translation initiation factor 4A3 (EIF4A3) promoted increased expression of circ_0022382 in breast cancer cells. In conclusion, EIF4A3-induced circ_0022382 regulates the expression of SLC7A11 proteins and related proteins in the PI3K-AKT signaling pathway by sponging let-7a-5p, which affects glucose metabolism and induces the death of breast cancer cells. Therefore, circ_0022382 may be useful as a marker or therapeutic agent in breast cancer treatment.