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. 2025 Nov 26.
doi: 10.1007/s13258-025-01714-y. Online ahead of print.

MicroRNA-124 induces AML differentiation and apoptosis through c-Myc suppression

Byeol-Eun Jeon #  1 , Chan-Seong Kwon #  1 , Ji-Eun Lee #  1 , Su-Ji Lee  1 , Kwonwoo Song  2 , Yun Ju Lee  1   3 , Du Hyeong Lee  1   3 , Sang-Woo Kim  4   5   6
Affiliations

MicroRNA-124 induces AML differentiation and apoptosis through c-Myc suppression

Byeol-Eun Jeon et al. Genes Genomics. .

Abstract

Background: Acute myeloid leukemia (AML) is a hematologic malignancy marked by blocked differentiation and uncontrolled proliferation. While miR-124 has been implicated as a tumor suppressor in various cancers, its functional role in AML remains unclear.

Objective: This study aimed to investigate the anti-leukemic effects of miR-124 and its regulatory mechanisms involving c-Myc and ROS signaling in AML.

Methods: AML cells were engineered to overexpress miR-124. Functional assays including flow cytometry, viability, and apoptosis analyses were conducted. ROS levels were measured, and c-Myc regulation was evaluated via western blotting, qPCR, ChIP, and pharmacological inhibition. Exosome-mediated delivery was also examined.

Results: miR-124 overexpression induced AML cell differentiation and apoptosis, accompanied by ROS accumulation and c-Myc downregulation. ROS induction suppressed c-Myc and activated the p21/p16/Rb axis, promoting cell cycle arrest. ChIP assays revealed that c-Myc binds the miR-124 promoter, indicating a negative feedback loop. Combination treatment with miR-124 and a c-Myc inhibitor enhanced anti-proliferative effects. Additionally, miR-124-containing exosomes reduced AML cell viability.

Conclusions: miR-124 acts as a tumor suppressor in AML by modulating a ROS-dependent c-Myc signaling pathway and inducing differentiation and apoptosis. These findings highlight miR-124 as a promising therapeutic and prognostic target in AML.

Keywords: AML differentiation; Acute myeloid leukemia; MicroRNA-124; Reactive oxygen species (ROS); c-Myc.

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Conflict of interest statement

Declarations. Conflict of interest: The authors confirm that they have no conflicts of interest. Ethical approval: Not applicable. Informed consent: Not applicable.

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