circATAD2 mitigates CD8+ T cells antitumor immune surveillance in breast cancer via IGF2BP3/m6A/PD-L1 manner

Abstract

Immune surveillance and chemotherapy sensitivity play critical functions in the tumorigenesis of breast cancer (BC). Emerging findings have indicated that circular RNA (circRNA) and N⁶-methyladenosine (m⁶A) both participate in the BC tumorigenesis. Here, present study aimed to investigate the roles of m⁶A-modified circATAD2 on BC and explore better understanding for BC precision therapeutic. Results reported that m⁶A-modifid circRNA (m⁶A-circRNA) microarray revealed the m⁶A-circRNA landscape in BC. M⁶A-modifid circATAD2 upregulated in BC samples and was closely correlated to poor prognosis. Functionally, circATAD2 promoted the immune evasion of BC cells and reduced the CD8⁺ T cells' killing effect. Mechanistically, MeRIP-seq unveiled the m⁶A modification in the 3'-UTR of PD-L1 mRNA, which was bound by circATAD2 and recognized by m⁶A reader IGF2BP3 to enhance PD-L1 mRNA stability and expression. In summary, these findings revealed the circATAD2/m⁶A/IGF2BP3/PD-L1 axis in BC immune surveillance, suggesting the potential that circATAD2 as a potential target for PD-L1-mediated BC.

Keywords: Breast cancer; Immune surveillance; N6-methyladenosine; PD-L1; circATAD2.