circATAD2 mitigates CD8+ T cells antitumor immune surveillance in breast cancer via IGF2BP3/m6A/PD-L1 manner
Zhiling Zhang, Wenjie Huo, Jie Li
Abstract
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 N 6 -methyladenosine (m 6 A) both participate in the BC tumorigenesis. Here, present study aimed to investigate the roles of m 6 A-modified circATAD2 on BC and explore better understanding for BC precision therapeutic. Results reported that m 6 A-modifid circRNA (m 6 A-circRNA) microarray revealed the m 6 A-circRNA landscape in BC. M 6 A-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 m 6 A modification in the 3’-UTR of PD-L1 mRNA, which was bound by circATAD2 and recognized by m 6 A reader IGF2BP3 to enhance PD-L1 mRNA stability and expression. In summary, these findings revealed the circATAD2/m 6 A/IGF2BP3/PD-L1 axis in BC immune surveillance, suggesting the potential that circATAD2 as a potential target for PD-L1-mediated BC.