MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers

Eur J Med Res. 2024 Jan 27;29(1):79. doi: 10.1186/s40001-024-01684-z.

Abstract

MDM4 is one of the MDM protein family and is generally recognized as the key negative regulator of p53. As a cancer-promoting factor, it plays a non-negligible role in tumorigenesis and development. In this article, we analyzed the expression levels of MDM4 in pan-cancer through multiple databases. We also investigated the correlations between MDM4 expression and prognostic value, immune features, genetic mutation, and tumor-related pathways. We found that MDM4 overexpression is often accompanied by adverse clinical features, poor prognosis, oncogenic mutations, tumor-immune infiltration and aberrant activation of oncogenic signaling pathways. We also conducted transcriptomic sequencing to investigate the effect of MDM4 on transcript levels in colon cancer and performed qPCR to verify this. Finally, we carried out some in vitro experiments including colony formation assay, chemoresistance and senescence-associated β-galactosidase activity assay to study the anti-tumor treatment effect of small molecule MDM4 inhibitor, NSC146109. Our research confirmed that MDM4 is a prognostic biomarker and potential therapeutic target for a variety of malignancies.

Keywords: Inhibitor; MDM4; Pan-cancer; Prognostic biomarker; Tumor-immune infiltration.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Cycle Proteins / metabolism
  • Humans
  • Nuclear Proteins* / genetics
  • Prognosis
  • Proto-Oncogene Proteins* / genetics
  • Proto-Oncogene Proteins* / metabolism
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Proto-Oncogene Proteins
  • Nuclear Proteins
  • Cell Cycle Proteins
  • Tumor Suppressor Protein p53
  • MDM4 protein, human