CLSPN is a potential biomarker associated with poor prognosis in low-grade gliomas based on a multi-database analysis

Jia, Yongsheng; Cheng, Xingbo; Liang, Wenjia; Lin, Shaochong; Li, Pengxu; Yan, Zheng‐Guang; Zhang, Meng; Ma, Wei; Hu, Chenchen; Wang, Baoya; Liu, Zhendong

doi:10.1016/j.retram.2022.103345

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…Higher CLSPN mRNA expression is related to a poorer prognosis in lung cancer [28]. Other studies have revealed that CLSPN is overexpressed in gastric cancer, renal cell carcinoma, prostate cancer, bladder cancer, and low-grade glioma [21,[29][30][31][32]. CLSPN protein expression is highest in the S phase, and in the G2/M phase, CLSPN is phosphorylated by PLK1 to induce protein degradation by the ubiquitinproteasome system [22,33].…”

Section: Discussionmentioning

confidence: 99%

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Yamada

Miyata

Isono

et al. 2023

Cancer Immunol Immunother

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Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a signi cant negative impact on prognosis. Thus, a treatment strategy for cisplatin-resistant bladder cancer is essential to improve the prognosis. In this study, we established a cisplatin-resistant (CR) bladder cancer cell line using a urothelial carcinoma cell line (UM-UC-3 cells). We screened for potential targets in CR cells and found that claspin (CLSPN) was overexpressed. CLSPNmRNA knockdown revealed that CLSPN had a role in cisplatin resistance in CR cells. In our previous study, we identi ed human leukocyte antigen (HLA)-A*02:01-restricted CLSPN peptide by HLA ligandome analysis. Thus, we generated a CLSPN peptide-speci c cytotoxic T lymphocyte (CTL) clone that recognized CR cells at a higher level than wild-type UM-UC-3 cells. These ndings indicate that CLSPN is a driver of cisplatin resistance and CLSPN peptide-speci c immunotherapy may be effective for cisplatin-resistant cases.

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Section: Discussionmentioning

confidence: 99%

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Yamada

Miyata

Isono

et al. 2023

Cancer Immunol Immunother

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Regulation of ATR–CHK1 signaling by ubiquitination of CLASPIN

Zhu

Zheng

Gong

et al. 2022

Biochemical Society Transactions

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DNA replication forks are frequently forced into stalling by persistent DNA aberrations generated from endogenous or exogenous insults. Stalled replication forks are catastrophic for genome integrity and cell survival if not immediately stabilized. The ataxia–telangiectasia and RAD3-related kinase (ATR)–CLASPIN-checkpoint kinase 1 (CHK1) signaling cascade is a pivotal mechanism that initiates cell-cycle checkpoints and stabilizes stalled replication forks, assuring the faithful duplication of genomic information before entry into mitosis. The timely recovery of checkpoints after stressors are resolved is also crucial for normal cell proliferation. The precise activation and inactivation of ATR–CHK1 signaling are usually efficiently regulated by turnover and the cellular re-localization of the adaptor protein CLASPIN. The ubiquitination–proteasome-mediated degradation of CLASPIN, driven by APC/CCDH1 and SCFβTrCP, results in a cell-cycle-dependent fluctuation pattern of CLASPIN levels, with peak levels seen in S/G2 phase when it functions in the DNA replisome or as an adaptor protein in ATR–CHK1 signaling under replication stress. Deubiquitination mediated by a series of ubiquitin-specific protease family proteins releases CLASPIN from proteasome-dependent destruction and activates the ATR–CHK1 checkpoint to overcome replication stress. Moreover, the non-proteolytic ubiquitination of CLASPIN also affects CHK1 activation by regulating CLASPIN localization. In this review, we discuss the functions of CLASPIN ubiquitination with specific linkage types in the regulation of the ATR–CHK1 signaling pathway. Research in this area is progressing at pace and provides promising chemotherapeutic targets.

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mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis

Liu,

2024

Preprint

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In single-cell data analysis, addressing sparsity often involves aggregating the profiles of homogeneous single cells into metacells. However, existing metacell partitioning methods lack checks on the homogeneity assumption and may aggregate heterogeneous single cells, potentially biasing down- stream analysis and leading to spurious discoveries. To fill this gap, we introduce mcRigor, a statistical method to detect dubious metacells, which are composed of heterogeneous single cells, and optimize the hyperparameter of a metacell partitioning method. The core of mcRigor is a feature-correlation-based statistic that measures the heterogeneity of a metacell, with its null distribution derived from a double permutation mechanism. As an optimizer for existing metacell partitioning methods, mcRigor has been shown to improve the reliability of discoveries in single-cell RNA-seq and multiome (RNA+ATAC) data analyses, such as uncovering differential gene co-expression modules, enhancer-gene associations, and gene temporal expression. Moreover, mcRigor enables benchmarking and selection of the most suitable metacell partitioning method with optimized hyperparameters tailored to specific datasets, ensuring re- liable downstream analysis. Our results showed that MetaCell and SEACells consistently outperformed MetaCell2 and SuperCell, though their superior performance comes at the expense of longer runtimes.

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CLSPN is a potential biomarker associated with poor prognosis in low-grade gliomas based on a multi-database analysis

Cited by 4 publications

References 40 publications

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma

Regulation of ATR–CHK1 signaling by ubiquitination of CLASPIN

mcRigor: a statistical method to enhance the rigor of metacell partitioning in single-cell data analysis

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