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Comprehensive Analysis Reveals Midnolin as a Potential Prognostic, Therapeutic, and Immunological Cancer Biomarker
Xin-Guo Zhang1,2, Wen-Ting Li1,2, Xin Jin2
1Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Biomedicines
|February 26, 2025
Summary
Midnolin (MIDN) regulates protein degradation and its expression is altered in many cancers. MIDN shows prognostic value and correlates with the tumor immune microenvironment, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Midnolin (MIDN) is a newly identified regulator of ubiquitin-independent proteasomal degradation.
- Understanding MIDN's role in cancer is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To comprehensively analyze the expression, prognostic significance, genomic alterations, interacting proteins, and immune microenvironment correlations of MIDN across various cancers.
- To investigate the functional role of MIDN in breast and gastric cancer cells.
Main Methods:
- Utilized public databases (GTEx, Depmap, GEPIA2, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA, DAVID, Human Protein Atlas, Sangerbox 3.0) for pan-cancer analysis.
- Performed immunofluorescence, qRT-PCR, and Western blotting to assess MIDN's biological functions in vitro.
- Analyzed correlations with tumor immune microenvironment, stemness, mutations, and RNA modification genes.
Main Results:
- MIDN expression is dysregulated in numerous cancers and serves as a prognostic marker in some, like esophageal cancer.
- MIDN mutations, primarily deep deletions, occur in 1.7% of cancers; NR4A1, PSMC1, and EGR1 are identified interacting proteins.
- MIDN levels correlate significantly with immune cell infiltration (CD8+ T cells, B cells, macrophages, etc.) and immune checkpoint genes (e.g., VEGFA) in specific cancers.
- MIDN downregulation in breast and gastric cancer cells affects cell proliferation, stemness, and upregulates FTO protein expression.
Conclusions:
- MIDN exhibits significant expression changes, prognostic value, and interactions within the tumor immune microenvironment across various cancers.
- MIDN presents potential as a novel therapeutic target and a prognostic biomarker for cancer treatment.
