Circ-RERE promotes autophagy and immune escape in acute myeloid leukemia involving the miR-128-3p/ZEB1/PD-L1 axis.

OBJECTIVE: To explore the role of circular RNA derived from RERE (circ-RERE) in regulating Programmed Death-Ligand-1 (PD-L1) expression and microRNA-128-3p (miR-128-3p)/Zinc finger e-box Binding homeobox-1 (ZEB1) axis in Acute Myeloid Leukemia (AML). METHODS: AML cell viability, proliferation, apoptosis, the ratio of microtubule-associated protein 1A/1B-Light Chain 3-phosphatidylethanolamine conjugate (LC3-II) to free LC3 (LC3-I) (LC3-II/LC3-I), and PD-L1 expression, as well as CD8(+)T-cell cytotoxicity, were correspondingly analyzed. The targeting relationship between miR-128-3p and circ-RERE or ZEB1 was verified. RESULTS: As detected, suppressing circ-RERE or overexpressing miR-128-3p significantly blocked the proliferation, migration, invasion, and autophagy of AML cells, promoted cell apoptosis, suppressed PD-L1 expression, and increased CD8+ T-cell cytotoxicity. circ-RERE competed with miR-128-3p to regulate ZEB1. Forced expression of ZEB1 did a reversal of circ-RERE suppression-induced effects. CONCLUSION: In a word, circ-RERE promotes autophagy and immune escape in AML by regulating PD-L1 expression through the miR-128-3p/ZEB1 axis, which may provide a new target for AML therapy.