A non-coding RNA circGNAI2 suppresses triple-negative breast cancer progression by sponging miR-454-3p to inhibit the VGLL4-STAT3 signaling

Circular RNAs (circRNAs), a novel group of non-coding RNAs, have been involved in the occurrence and development of different malignancies. However, the potential functional role of circRNAs in triple-negative breast cancer (TNBC) remains largely unknown, we aimed to investigate the regulatory functions and underlying mechanism of a conserved circRNA, circGNAI2, in TNBC. In this study, we demonstrated that circGNAI2 was aberrantly downregulated in TNBC cells and was negatively associated with poor prognosis. Functional experiments showed that circGNAI2 significantly suppressed TNBC cell proliferation and migration in vivo and in vitro. Mechanistically, we found that circGNAI2 upregulated VGLL4 and inhibited the phosphorylation STAT3 by sponging miR-454-3p. Moreover, EIF4A3 has binding sites in the upstream region of the GNAI2 pre-mRNA, and we confirmed that circGNAI2 was downregulated by EIF4A3 in TNBC cells. Overall, our study indicates that EIF4A3-regulated circGNAI2 suppresses TNBC progression possibly by regulating the miR-454-3p/VGLL4/STAT3 pathway, providing pivotal potential therapeutic targets for the treatment of TNBC.