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Published on: April 21, 2022
NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine
He-Liang Wu1, Zhi-Ran Yang2, Li-Jun Yan2
1Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Peking University Ninth School of Clinical Medicine, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, 100038, China.
Background:
This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets.
Methods:
NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein.
Results:
The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM.
Conclusion:
NPM2 may play a key role in the development and progression of MPM.
Insights
Nucleoplasmin 2 (NPM2) protein structure and gene biology are linked to malignant peritoneal mesothelioma (MPM). High NPM2 expression correlates with lower survival rates in MPM patients, suggesting NPM2 as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Oncology
- Structural Biology
Background:
- Nucleoplasmin 2 (NPM2) is a protein with known gene biology features and structural domains.
- Its role in malignant peritoneal mesothelioma (MPM) is under investigation to understand the disease's molecular pathology.
Purpose of the Study:
- To systematically review NPM2 gene biology and protein structure.
- To elucidate the relationship between NPM2 and MPM.
- To identify potential new therapeutic targets for MPM.
Main Methods:
- Literature search of the NCBI PubMed database.
- Review of gene and protein databases (NCBI Gene, Protein, Ensembl, UniProt, RCSB PDB).
- Bioinformatic analysis using online tools (Consurf, DoGSiteScorer, ZdockServer) and databases (GEPIA, TCGA).
Main Results:
- NPM2 protein features conserved N-terminal core region for histone binding and a C-terminal acidic tract.
- NPM2 expression correlates with multiple tumor pathologies; high NPM2 expression is linked to decreased 5-year survival in MPM patients.
- NPM2 facilitates histone deacetylation, potentially inhibiting gene transcription and promoting MPM proliferation, invasion, and metastasis.
Conclusions:
- NPM2 plays a significant role in the development and progression of malignant peritoneal mesothelioma.
- Targeting NPM2 may offer a novel therapeutic strategy for MPM.
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