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

TL;DR

This study shows that circ-RERE helps AML cells avoid immune detection by boosting autophagy and PD-L1 through a specific molecular pathway.

Contribution

The study identifies a novel regulatory mechanism involving circ-RERE, miR-128-3p, ZEB1, and PD-L1 in AML.

Findings

circ-RERE promotes autophagy and immune escape in AML cells.

miR-128-3p inhibits autophagy and immune escape by targeting ZEB1.

ZEB1 upregulation reverses the effects of circ-RERE suppression.

Abstract

•circ-RERE is augmented in AML.•Silencing circ-RERE can inhibit autophagy and immune escape in AML cells.•circ-RERE is a molecular sponge for miR-128–3p.•miR-128–3p can block autophagy and immune escape in AML cells.•Up-regulation of ZEB1 reverses the effect of down-regulation of circ-RERE on AML cells.

circ-RERE is augmented in AML.

Silencing circ-RERE can inhibit autophagy and immune escape in AML cells.

circ-RERE is a molecular sponge for miR-128–3p.

miR-128–3p can block autophagy and immune escape in AML cells.

Up-regulation of ZEB1 reverses the effect of down-regulation of circ-RERE on AML cells.

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).

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.

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.

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.

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