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

  • Genes Genomics. 2025 Nov 26. doi: 10.1007/s13258-025-01714-y.
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
  • 1. Department of Integrated Biological Science, College of Natural Sciences, Pusan National University, Busan, 46241, Republic of Korea.
  • 2. Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
  • 3. Institute of Systems Biology, Pusan National University, Busan, 46241, Republic of Korea.
  • 4. Department of Integrated Biological Science, College of Natural Sciences, Pusan National University, Busan, 46241, Republic of Korea. [email protected].
  • 5. Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 46241, Republic of Korea. [email protected].
  • 6. Department of Biological Sciences, Pusan National University, Busan, 609-735, Republic of Korea. [email protected].
  • # Contributed equally.
PMID: 41296171 DOI: 10.1007/s13258-025-01714-y
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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