bims-midomi Biomed News
on MDM2 and mitochondria
Issue of 2025–07–27
two papers selected by
Gavin McStay, Liverpool John Moores University



  1. Curr Issues Mol Biol. 2025 May 08. pii: 338. [Epub ahead of print]47(5):
      As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, a selective Histone deacetylase 6 (HDAC6) inhibitor, and its mechanism targeting p53 regulation. In vitro studies conducted with HepG2 and SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, and invasive potential, as evidenced by CCK-8, colony formation, and Transwell assays. Furthermore, ACY-1215 induced caspase-dependent apoptosis. Mechanistically, ACY-1215 enhanced p53 acetylation by disrupting HDAC6-p53 interaction, thereby stabilizing p53 protein levels. Concurrently, it inhibited Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking proteasomal degradation and prolonging p53 half-life. This dual modulation restored p53 transcriptional activity, leading to the upregulation of downstream effector molecules associated with cell cycle regulation and apoptosis. Collectively, our findings reveal that ACY-1215 exerts potent anti-HCC effects through coordinated regulation of p53 acetylation and ubiquitination, offering a novel dual-targeting strategy for HCC therapy.
    Keywords:  MDM2 protein; acetylation; hepatocellular carcinoma; histone deacetylase 6; p53; ubiquitination
    DOI:  https://doi.org/10.3390/cimb47050338
  2. Curr Pharm Des. 2025 Jul 23.
       INTRODUCTION: Genetic factors play a significant role in the development of leukemia. The overexpression of MDM2 is associated with the progression of certain leukemias. This meta-analysis investigates the relationship between the MDM2 SNP 309T>G and various forms of leukemia across global populations.
    METHODS: A comprehensive literature search was conducted to retrieve genotyping data from twenty casecontrol studies related to MDM2 SNP 309T>G polymorphism and leukemia. A random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association analysis. MetaGenyo software was utilized to conduct statistical analyses in this meta-analysis.
    RESULTS: The findings indicate a significant association between MDM2 309 SNPT>G polymorphism and leukemia in Asian and Caucasian populations. Additionally, this polymorphism is associated with an increased risk of Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), implying that MDM2 may play a role in the pathogenesis of these specific forms of leukemia.
    CONCLUSION: This meta-analysis suggests that MDM2 may represent a susceptibility gene for leukemia risk.
    Keywords:  AML; CML.; MDM2 309 SNP T>G; leukemia; meta-analysis; rs2279744
    DOI:  https://doi.org/10.2174/0113816128368759250527073556