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MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers
Jie Liu1,2,3, Jie Yang2,3, Qilong Pan1
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
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.
Insights
MDM4 protein, a cancer promoter, is overexpressed in many cancers, correlating with poor prognosis and activated oncogenic pathways. Inhibiting MDM4 shows anti-tumor effects, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- MDM4 (MDM4 protein) is a key negative regulator of the tumor suppressor p53.
- MDM4 functions as a cancer-promoting factor in tumorigenesis and development.
Purpose of the Study:
- To analyze MDM4 expression across various cancers using multiple databases.
- To investigate the relationship between MDM4 expression and clinical features, prognosis, immune infiltration, genetic mutations, and cancer pathways.
- To evaluate the anti-tumor potential of a small molecule MDM4 inhibitor.
Main Methods:
- Pan-cancer analysis of MDM4 expression levels via public databases.
- Correlation analyses between MDM4 expression and prognostic, immune, genetic, and pathway data.
- Transcriptomic sequencing in colon cancer to assess MDM4's transcriptomic effects.
- Quantitative PCR (qPCR) for verification.
- In vitro assays (colony formation, chemoresistance, senescence-associated β-galactosidase) to test MDM4 inhibitor NSC146109 efficacy.
Main Results:
- MDM4 overexpression is linked to adverse clinical features and poor prognosis in pan-cancer.
- Elevated MDM4 correlates with increased tumor-immune infiltration and aberrant activation of oncogenic signaling pathways.
- Transcriptomic analysis revealed MDM4's impact on gene expression in colon cancer.
- In vitro studies demonstrated the anti-tumor effects of the MDM4 inhibitor NSC146109, including reduced chemoresistance and induced senescence.
Conclusions:
- MDM4 is a significant prognostic biomarker across a variety of malignancies.
- MDM4 represents a potential therapeutic target for cancer treatment.
- Targeting MDM4 with inhibitors like NSC146109 may offer a viable anti-cancer strategy.
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