The mechanism underlying the oncogenic potential of AAA+ ATPase PSMC4 in cancer is revealed by mutations and copy number amplifications

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis Pub Date : 2025-01-01 DOI:10.1016/j.mrfmmm.2025.111901

Sanjida Mallick , Qurratulain Qamar , Bibhudutta Mishra , Aditi Nayak

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引用次数: 0

Abstract

Recent research has discovered a connection between the AAA+ ATPase PSMC4 (Proteasome 26S Subunit, ATPase 4) and several forms of cancer. However, a detailed analysis of the oncogenic potential of PSMC4 was elusive. In this study, we anticipate PSMC4's potential as a cancer biomarker. We aimed to comprehensively assess the expression profiles, prognostic significance, and relevant cellular pathways associated with it. Through our examination of various types of cancers, PSMC4 is found to be overexpressed. Interestingly, our result finds a positive correlation between PSMC4 overexpression and unfavourable overall survival rates in cancer. Further, we looked into the mutations and copy number amplifications of PSMC4 across various cancers. Our study reveals that missense mutations plays a great role behind the oncogenic potential of PSMC4. Several possible mutation sites are predicted. Interestingly, we found fifteen hotspot mutations in the ATPase domain of PSMC4. Additionally, PSMC4 has shown a high amplification percentage in various cancers. We are additionally attentive to the functional characteristics of the protein PSMC4 across various types of cancer. In the protein-protein interaction analyses, it was found that multiple oncoproteins were directly interacting with PSMC4. The top signaling pathways of PSMC4 also indicate that it plays a crucial role in cancer development. Overall, this study reveals that PSMC4 could be a potential diagnostic and prognostic marker for cancer, making it a promising biomarker and target.

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来源期刊

Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 生物-毒理学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

51 days

期刊介绍： Mutation Research (MR) provides a platform for publishing all aspects of DNA mutations and epimutations, from basic evolutionary aspects to translational applications in genetic and epigenetic diagnostics and therapy. Mutations are defined as all possible alterations in DNA sequence and sequence organization, from point mutations to genome structural variation, chromosomal aberrations and aneuploidy. Epimutations are defined as alterations in the epigenome, i.e., changes in DNA methylation, histone modification and small regulatory RNAs. MR publishes articles in the following areas: Of special interest are basic mechanisms through which DNA damage and mutations impact development and differentiation, stem cell biology and cell fate in general, including various forms of cell death and cellular senescence. The study of genome instability in human molecular epidemiology and in relation to complex phenotypes, such as human disease, is considered a growing area of importance. Mechanisms of (epi)mutation induction, for example, during DNA repair, replication or recombination; novel methods of (epi)mutation detection, with a focus on ultra-high-throughput sequencing. Landscape of somatic mutations and epimutations in cancer and aging. Role of de novo mutations in human disease and aging; mutations in population genomics. Interactions between mutations and epimutations. The role of epimutations in chromatin structure and function. Mitochondrial DNA mutations and their consequences in terms of human disease and aging. Novel ways to generate mutations and epimutations in cell lines and animal models.

The mechanism underlying the oncogenic potential of AAA+ ATPase PSMC4 in cancer is revealed by mutations and copy number amplifications

Abstract

The mechanism underlying the oncogenic potential of AAA+ ATPase PSMC4 in cancer is revealed by mutations and copy number amplifications