bims-midomi Biomed News
on MDM2 and mitochondria
Issue of 2026–01–04
six papers selected by
Gavin McStay, Liverpool John Moores University
  1. Genetic susceptibility to retinoblastoma: A meta-analysis of single-nucleotide polymorphisms across global populations.
  2. A Small Indole Derivative Isolated From Caper (Capparis ovata) as an Inducer of P53-Mediated Apoptosis in Prostate Cancer: Comprehensive In Vitro and In Silico Studies.
  3. Myxoid Pleomorphic Liposarcoma: A Review and Update.
  4. Discovery of Histone Deacetylase 8-Specific Proteolysis-Targeting Chimeras with Anticancer Activity against Hematological Malignancies.
  5. RAB18 is upregulated in colorectal cancer and promotes tumor progression.
  6. From Validation to Refinement: Optimising a Diagnostic Score for Atypical Lipomatous Tumours and Lipomas.
  1. J Cancer Res Ther. 2025 Oct 01. 21(7): 1286-1297
    Genetic susceptibility to retinoblastoma: A meta-analysis of single-nucleotide polymorphisms across global populations.
    Shobhit Gupta, Deepsekhar Das, Sushma Nandyala, Tapas Kumar Roy, Udita Tiwari.
       ABSTRACT: The effect of single-nucleotide polymorphisms (SNPs) in Cyclin Dependent Kinase Inhibitor 1A (CDKN1A C/A), Mouse Double Minute 2 (MDM2), 309 T/G methylenetetrahydrofolate reductase (MTHFR) 677 C/T, MTHFR 1298 A/C, and Methionine synthase (MTR) 2756 A/G has been investigated in retinoblastoma (RB) with inconsistent results. Therefore, this study aims to conduct a meta-analysis and explore the overall role of these genetic variants with retinoblastoma risk. Literature search was done using PubMed, EMBASE, Cochrane Library, Google, Dogpile, and CBM all studies evaluating the association between CDKN1A or p21 C/A, MDM2 309 T/G, MTHFR 677 C/T, MTHFR 1298 A/C, and MTR 2756 A/G polymorphism and RB risk were included. A total of 1773 patients and 2474 controls were included. To understand these polymorphisms' role in RB risk, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random or fixed effects model. P values < 0.05 were considered statistically significant. Funnel plots were used to assess publication bias. Our meta-analysis showed a significant association between RB susceptibility to CDKN1A dominant model (OR = 1.518, 95% CI = 1.003-2.298, P = 0.048), MDM2 dominant model (OR = 0.700, 95% CI = 0.542-0.903, P = 0.006) and MTR 2756 A/G all models that is allele model (OR = 4.680, 95% CI = 1.992-10.993, P = 0.000), dominant model (OR = 2.044, 95% CI = 1.511-2.765, P = 0.000), and recessive model (OR = 0.283, 95% CI = 0.122-0.656, P = 0.003). The present meta-analysis suggested that MTR 2756 A/G, MDM2 309 T/G, and CDKN1A polymorphism are associated with the risk of RB.
    Keywords:  CDKN1A and meta-analysis; MDM2; MTR; polymorphism; retinoblastoma
    DOI:  https://doi.org/10.4103/jcrt.jcrt_456_25
  2. J Biochem Mol Toxicol. 2026 Jan;40(1): e70666
    A Small Indole Derivative Isolated From Caper (Capparis ovata) as an Inducer of P53-Mediated Apoptosis in Prostate Cancer: Comprehensive In Vitro and In Silico Studies.
    Özden Özgün Acar, Işıl Gazioğlu, Hatice Oruç, Elif Kale, Halil Şenol, Gülaçtı Topçu, Alaattin Şen.
      Natural products with stunning chemical diversity have been extensively researched for their anticancer potential for more than fifty years. This study aimed to determine the effect of indole derivative 1H-indole-2-hydroxy-3-carboxylic acid (IHCA), isolated as a novel alkaloid from Capparis ovata, on selected tumor suppressor, apoptotic, and cell cycle regulatory genes, which are known to be important in cancer pathophysiology, on Caco-2 and LNCaP cells in comparison with Taxol. The molecular mechanism of IHCA's anticancer activity is essentially undefined. Different concentrations of IHCA increased the expression levels of apoptosis-related genes, including BCL-2 and TNF-α. In addition, the tumor suppressor genes PTEN, P53, and RB were increased in LNCaP and Caco-2 cells. KRAS, an oncogenic gene, was significantly downregulated by IHCA in LNCaP cells. Western blot results showed that the protein expression levels of P53 and PTEN in LNCaP cells were increased when treated with IHCA, whereas CDK4 and TNF-α were decreased. Finally, IHCA and doxorubicin significantly increased P53-driven luciferase activity compared to the control. The results strongly suggest that the novel natural compound IHCA has an anticancer effect involving the regulation of the P53 gene and its networks in vitro. The molecular docking and MD simulation analyses reveal that IHCA exhibits superior binding potential to the MDM2 protein compared to Nutlin-3a. MD simulations further confirm that IHCA maintains a more stable and consistent interaction with MDM2, as indicated by lower RMSD values and reduced ligand fluctuation. These results highlight IHCA's potential as a more effective MDM2 inhibitor, suggesting its promise as a lead compound for anticancer drug development. Clinical Trial Registration: Not applicable.
    Keywords:  Indole‐2‐hydroxy‐3‐carboxylic acid; P53; anti‐cancer; molecular docking; molecular dynamics
    DOI:  https://doi.org/10.1002/jbt.70666
  3. Cancer Genomics Proteomics. 2026 Jan-Feb;23(1):23(1): 1-11
    Myxoid Pleomorphic Liposarcoma: A Review and Update.
    Jun Nishio, Shizuhide Nakayama, Mikiko Aoki.
      Myxoid pleomorphic liposarcoma (MPLPS) is an exceedingly rare and recently recognized adipocytic neoplasm that primarily occurs in children and young adults and shows a strong predilection for the mediastinum. Clinically, MPLPS demonstrates aggressive behavior and exhibits a high propensity for systemic spread and a worse overall survival. Some cases have been associated with Li-Fraumeni syndrome. Histologically, MPLPS is composed of a variable mixture of myxoid and pleomorphic liposarcoma-like components. Immunohistochemically, the tumor cells show diffuse expression of CD34 and p16 and loss of nuclear RB expression. MPLPS lacks DNA damage inducible transcript 3 (DDIT3) rearrangements and MDM2 proto-oncogene (MDM2) amplifications but shows tumor protein p53 (TP53) mutations and RB transcriptional co-repressor 1 (RB1) deletions. Moreover, recent studies have demonstrated that the most consistent molecular feature of MPLPS is genome-wide loss of heterozygosity. Surgical excision with negative margins is the mainstay of treatment for localized MPLPS. The treatment of advanced/metastatic MPLPS still poses a huge therapeutic challenge. This review provides information about the clinicoradiological features, pathogenesis, histopathology, and management currently available for MPLPS. In addition, we discuss the differential diagnosis of this novel entity.
    Keywords:  Myxoid pleomorphic liposarcoma; RB1; TP53; atypical spindle-cell/pleomorphic lipomatous tumor; dedifferentiated liposarcoma; myxoid liposarcoma; pleomorphic liposarcoma; review; treatment
    DOI:  https://doi.org/10.21873/cgp.20557
  4. J Med Chem. 2026 Jan 02.
    Discovery of Histone Deacetylase 8-Specific Proteolysis-Targeting Chimeras with Anticancer Activity against Hematological Malignancies.
    Shiyang Zhai, Marie Kemkes, Cindy-Esther Kponomaizoun, Jan Gerhartz, Felix Feller, Jia-Wey Tu, Dominika Ewa Pieńkowska, Julian Schliehe-Diecks, Ina Dressel, Michael Gütschow, Radosław P Nowak, Christian Steinebach, Sanil Bhatia, Finn K Hansen.
      Histone deacetylase 8 (HDAC8) has emerged as promising therapeutic target for several malignancies. In this study, we developed two series of cereblon (CRBN)-recruiting proteolysis-targeting chimeras (PROTACs) for targeted HDAC8 degradation, utilizing the selective HDAC8 inhibitor PCI-34051 as warhead. The pomalidomide/thalidomide-based series (BP1-BP5) exhibited strong antiproliferative activity against leukemia and multiple myeloma cells, accompanied by degradation of CRBN neosubstrates. In contrast, the phenyl glutarimide-based series (BP6-BP10) displayed low cytotoxicity, no neosubstrate degradation, and enhanced chemical stability. The hit compounds from both series, BP1 (DC50, 24 h = 20 nM, Dmax, 24 h = 99%) and BP6 (DC50, 24 h = 81 nM, Dmax, 24 h = 93%), demonstrated highly efficient and selective HDAC8 degradation. Pretreatment with BP6 enhanced the tumor suppressor p53 stability, thereby significantly increasing the sensitivity of leukemia cells to the MDM2 antagonist idasanutlin than PCI-34051, highlighting its unique potential for combinatorial therapy without impacting neosubstrates.
    DOI:  https://doi.org/10.1021/acs.jmedchem.5c00939
  5. Pathol Res Pract. 2025 Dec 25. pii: S0344-0338(25)00536-9. [Epub ahead of print]278 156343
    RAB18 is upregulated in colorectal cancer and promotes tumor progression.
    Hao Cheng, Suzeng Wang, Chunyu Yang, Feiyu Qin, Mengyuan Qian, Heyuan Jia, Kaiqing Wang, Surui Yao, Zhaohui Huang, Bojian Fei.
      RAB18 (Ras-related protein Rab-18) plays a crucial role in diverse cellular processes including autophagy, secretion and lipid droplet biogenesis. Recent studies suggest that RAB18 participates in tumorigenesis and progression. However, its role in colorectal cancer (CRC) is unclear. In this study, we observed significantly increased RAB18 expression in CRC tissues compared with paired normal tissues, which was associated with poor prognosis. RAB18 knockdown significantly inhibited cell proliferation, cell cycle progression, migration and invasion in CRC cells. Moreover, silencing RAB18 expression suppressed tumorigenesis in a mouse xenografted CRC model. Mechanistically, RNA-seq and pathway enrichment analyses suggested that RAB18 knockdown induced p53 pathway activation and decreased levels of E2F Targets and G2M checkpoint genes. Further validation identified stratifin (SFN) and mouse double minute 2 (MDM2) as potential downstream mediators of RAB18's pro-tumorigenic effects in CRC. Collectively, our findings demonstrate the oncogenic role of RAB18 in CRC and highlight its potential as both a prognostic biomarker and a therapeutic target.
    Keywords:  Cell cycle; Colorectal cancer; MDM2; Proliferation; RAB18; SFN
    DOI:  https://doi.org/10.1016/j.prp.2025.156343
  6. Diagnostics (Basel). 2025 Dec 14. pii: 3190. [Epub ahead of print]15(24):
    From Validation to Refinement: Optimising a Diagnostic Score for Atypical Lipomatous Tumours and Lipomas.
    Wolfram Weschenfelder, Katharina Lucia Koeglmeier, Friederike Weschenfelder, Till Rosenkranz, Christian Spiegel, Sebastian Walter.
      Background/Objectives: Differentiating atypical lipomatous tumours (ALT) from lipomas remains challenging, as both share similar clinical and radiological features but require different forms of management. We previously proposed a clinical-radiological score integrating routine parameters to improve preoperative discrimination. This study aimed to externally validate the score in an independent cohort and refine it for enhanced robustness. Methods: We retrospectively analysed 119 patients with lipomatous tumours treated between 2022 and 2024 at an external university hospital. Diagnostic performance of the original models was assessed using receiver operating characteristic analysis. Data were then combined with the initial development cohort (n = 106) to recalibrate the models and define new cut-offs. Results: In the external validation cohort, predictive accuracy decreased compared to the derivation cohort, especially in extremity tumours assessed without contrast (AUC 0.830 vs. 0.942). Across four recalibrated models in the combined dataset (n = 225), diagnostic accuracy remained high (AUCs 0.918-0.954). Models combining clinical and imaging parameters consistently outperformed single-parameter approaches, with contrast enhancement providing the greatest incremental value. Accuracy was lower in trunk-localised tumours, highlighting the need for molecular confirmation in selected subgroups. Conclusions: The re-modelled score demonstrated robust diagnostic accuracy and practicality for routine use, offering a resource-efficient tool to support preoperative risk stratification. While molecular testing remains essential in high-risk cases, the refined score may reduce unnecessary testing and facilitate tailored diagnostic strategies. To support clinical adoption, the score is available as a web application that automatically selects the appropriate model and presents results in a colour-coded format.
    Keywords:  MDM2 amplification; MRI; atypical lipomatous tumour; lipoma; soft tissue tumour
    DOI:  https://doi.org/10.3390/diagnostics15243190
This page is being maintained by Thomas Krichel. It was last updated on 2026‒01‒04 at 12:18.