Role of circAGFG1 as an oncogene in triple-negative breast cancer.

Circular RNAs (circRNAs) have been identified as important mediators of tumorigenesis and tumor progression. This study focuses on circAGFG1, a circRNA with elevated N6-methyladenosine (m6A) modification, and its role in triple-negative breast cancer (TNBC). Fluorescence in situ hybridization and qPCR analyses revealed that circAGFG1 is significantly upregulated in TNBC tissues and in the TNBC cell line MDA-MB-231. Functional characterization using loss-of-function and gain-of-function strategies in two TNBC cell lines demonstrated that circAGFG1 promotes oncogenic phenotypes. Specifically, knockdown in MDA-MB-231 cells suppressed proliferation, invasion, migration, and G1/S phase transition, while its overexpression in MDA-MB-468 cells promoted these processes. Mechanistically, western blotting and PCR analyses indicated that circAGFG1 modulates the expression of epithelial-mesenchymal transition markers N-cadherin and α-SMA. Furthermore, we identified that YTHDF3, an m6A reader protein upregulated in TNBC, upregulates circAGFG1 expression by enhancing its transcript stability. Finally, dual-luciferase reporter assays confirmed that circAGFG1 acts as a sponge for miR-1299, thereby potentially modulating the miR-1299 signaling pathway. Collectively, our findings delineate the critical role of the circAGFG1 in promoting TNBC progression, highlighting its potential as a novel therapeutic target.