The HAUSP gene plays an important role in non‐small cell lung carcinogenesis through p53‐dependent pathways
Abstract
Herpesvirus‐associated ubiquitin‐specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de‐ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non‐small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction‐single‐strand conformation polymorphism (PCR‐SSCP) followed by sequencing. Quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty‐nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down‐regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild‐type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild‐type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53‐dependent pathways. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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USP7 is deregulated in many cancer types, and deviations in USP7 protein levels are correlated with cancer progression.
“USP7 is also deregulated in many cancer types, where deviances in USP7 protein levels are correlated with cancer progression.”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Masuya et al., 2006
USP7 gene expression is frequently downregulated in non-small cell lung adenocarcinomas, where low USP7 mRNA expression correlated with reduced p53 immunostaining.
“Consistent with this assessment, USP7 gene expression has been found to be frequently downregulated in non-small cell lung adenocarcinomas, where low USP7 mRNA expression correlated with reduced p53 immunostaining (Masuya et al., 2006).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Masuya et al., 2006
Low USP7 expression levels are an indicator of poor patient prognosis.
“Furthermore, low USP7 expression levels were found to be an indicator of poor patient prognosis, supporting a role for USP7 in suppressing cancer progression by maintaining genome stability (Masuya et al., 2006).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Masuya et al., 2006
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- Authors
- Masuya, D., Huang, C., Liu, D., Nakashima, T., Yokomise, H., Ueno, M., Nakashima, N., & Sumitomo, S.
- Affiliations
- Kagawa University (JP)
- Japanese Red Cross Society Wakayama Medical Center (JP)
- Corresponding author
- Huang, C
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2006-01-31
- Volume
- 208
- Issue
- 5
- Pages
- 724-732
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- OpenAlex
- W1968526688
- Cited by
- 103
- References
- 35
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 6 · 2012: 5
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- USP7, non-small cell lung cancer, p53, TP53 mutation, p21, Bax, MDM2, adenocarcinoma, squamous cell carcinoma, prognostic factors, tumour suppressor, carcinogenesis, p53 target genes, gene downregulation
- MeSH terms
- Ubiquitin-Specific Peptidase 7, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lung Neoplasms, Mutation, Neoplasm Proteins, Neoplasm Staging, Endopeptidases, RNA, Messenger, RNA, Neoplasm, Survival Analysis, Genes, p53, Tumor Suppressor Protein p53, Polymorphism, Single-Stranded Conformational, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin Thiolesterase, Cyclin-Dependent Kinase Inhibitor p21, bcl-2-Associated X Protein, Proto-Oncogene Proteins c-mdm2
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