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

IF 2.4 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Clinics Pub Date : 2026-01-01 Epub Date: 2026-03-20 DOI:10.1016/j.clinsp.2025.100850

XiaoWei Shi, TianTian Wang, KeYa Sha, ShuangYue Li, RenZhi Pei, Ying Lu

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引用次数: 0

Abstract

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.

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Circ-RERE参与miR-128-3p/ZEB1/PD-L1轴促进急性髓系白血病的自噬和免疫逃逸。

目的：探讨源自RERE的环状RNA （circ-RERE）在急性髓性白血病（AML）中调控程序性死亡配体-1 （PD-L1）表达和microRNA-128-3p (miR-128-3p)/锌指e-box Binding homeobox-1 （ZEB1）轴中的作用。方法：分析AML细胞活力、增殖、凋亡、微管相关蛋白1A/ 1b -轻链3-磷脂酰乙醇胺偶联物（LC3- ii）与游离LC3 (LC3- i) （LC3- ii /LC3- i）的比值、PD-L1表达以及CD8+ t细胞的细胞毒性。验证miR-128-3p与circ-RERE或ZEB1的靶向关系。结果：经检测，抑制circ-RERE或过表达miR-128-3p可显著阻断AML细胞的增殖、迁移、侵袭和自噬，促进细胞凋亡，抑制PD-L1表达，增加CD8+ t细胞的细胞毒性。circ-RERE与miR-128-3p竞争调控ZEB1。强制表达ZEB1逆转了circ-RERE抑制诱导的效应。结论：综上所述，circ-RERE通过miR-128-3p/ZEB1轴调控PD-L1表达，促进AML自噬和免疫逃逸，可能为AML治疗提供新的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics 医学-医学：内科

CiteScore

4.10

自引率

3.70%

发文量

129

审稿时长

52 days

期刊介绍： CLINICS is an electronic journal that publishes peer-reviewed articles in continuous flow, of interest to clinicians and researchers in the medical sciences. CLINICS complies with the policies of funding agencies which request or require deposition of the published articles that they fund into publicly available databases. CLINICS supports the position of the International Committee of Medical Journal Editors (ICMJE) on trial registration.