Hypomethylation-driven overexpression of HJURP promotes progression of hepatocellular carcinoma and is associated with poor prognosis

Li, Ye; Qu, Yi; Han, Chen; Li, Zheng; Li, Hui; Qian, Yu; Yan, Xuexin; Chen, Xinyu; Zhu, Huawei; Zhao, Bin; Lin, Qiulu; Liang, Li; Wang, Li; Qin, Fanghui; Xie, Weimin; Li, Yongqiang; Huang, Wenfeng

doi:10.1016/j.bbrc.2021.05.102

Cited by 15 publications

(16 citation statements)

References 15 publications

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“…This is consistent with the fact that HJURP is required for binding of CENP-A to centromeres during telophase/early G1 phase, which ensures proper chromosome separation during mitosis (8,28). This role may help explain how HJURP promotes the proliferation of HCC cells (17,29), through a mechanism involving activation of MAPK/ERK1/2 and AKT/GSK3β signaling pathways (13). We have further shown that polymorphism in HJURP influences risk of HCC among Chinese (30), and that the protein promotes HCC cell migration and invasion (17).…”

Section: Discussionsupporting

confidence: 83%

“…This role may help explain how HJURP promotes the proliferation of HCC cells (17,29), through a mechanism involving activation of MAPK/ERK1/2 and AKT/GSK3β signaling pathways (13). We have further shown that polymorphism in HJURP influences risk of HCC among Chinese (30), and that the protein promotes HCC cell migration and invasion (17). These considerations strongly suggest that HJURP acts via the cell cycle to promote hepatocyte proliferation and act as a proto-oncogene.…”

Section: Discussionmentioning

confidence: 66%

“…Our previous study showed that HJURP is overexpressed in HCC tissues, and that this overexpression is associated with worse survival (17). In the present work, we used GEPIA2 and TCGA-LIHC data to provide further evidence that HJURP is a proto-oncogene in HCC and an independent prognostic factor.…”

Section: Discussionmentioning

confidence: 87%

“…As a result, HJURP can participate in various cell proliferation-related pathways and promote the proliferation of tumor cells (11)(12)(13)(14)(15)(16). We previously reported that HJURP is more strongly expressed in HCC tissues than in adjacent normal tissues, and its high expression is a risk factor for poor prognosis in HCC patients (17). We also demonstrated that HJURP promotes HCC cell proliferation, migration, and invasion, while promoting progression through the cell cycle and apoptosis.…”

Section: Introductionmentioning

confidence: 88%

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Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis

Luo¹,

Liao²,

Liu³

et al. 2022

Pathol. Oncol. Res.

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Background: Hepatocellular carcinoma is the most common type of primary liver cancer, and it is associated with poor prognosis. It often fails to respond to immunotherapy, highlighting the need to identify genes that are associated with the tumor microenvironment and may be good therapeutic targets. We and others have shown that the Holliday cross-recognition protein HJURP can promote the proliferation, migration, and invasion by hepatocellular carcinoma cells, and that HJURP overexpression is associated with poor survival. Here we explored the potential relationship between HJURP and the tumor microenvironment in hepatocellular carcinoma.Methods: We used the Immuno-Oncology-Biological-Research (IOBR) software package to analyze the potential roles of HJURP in the tumor microenvironment. Using single-cell RNA sequencing data, we identified the cell clusters expressing abundant HJURP, then linked some of these clusters to certain bioprocesses using Gene Set Enrichment Analysis (GSEA). We validated the differential expression of HJURP in tumor-infiltrating CD8+ T cells, sorted by flow cytometry into populations based on the expression level of PD-1. We used weighted gene co-expression network analysis (WGCNA) to identify immunity-related genes whose expression strongly correlated with that of HJURP. The function of these genes was validated based on enrichment in Gene Ontology (GO) terms, and they were used to establish a prognosis prediction model.Results: IOBR analysis suggested that HJURP is significantly related to the immunosuppressive tumor microenvironment and was significantly related to T cells, dendritic cells, and B cells. Based on single-cell RNA sequencing, HJURP was strongly expressed in T cells, erythrocytes, and B cells from normal liver tissues, as well as in CD8+ T cells, dendritic cells, and one cluster of hepatocytes in hepatocellular carcinoma tissues. Malignant hepatocytes strongly expressing HJURP were associated with the downregulation of immune bioprocesses. HJURP expression was significantly higher in CD8+ T cells strongly expressing PD-1 than in those expressing no or intermediate levels of PD1. WGCNA identified two module eigengenes (comprising 397 and 84 genes) related to the tumor microenvironment. We identified 24 hub genes and confirmed that they were related to immune regulation. A prognostic risk score model based on expression of HJURP, PPT1, PML, and CLEC7A showed moderate ability to predict survival.Conclusion:HJURP is associated with tumor-infiltrating immune cells, immune checkpoints, and immune suppression in hepatocellular carcinoma. HJURP-related genes involved in immune responses may be useful for predicting patient prognosis.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 88%

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Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis

Luo¹,

Liao²,

Liu³

et al. 2022

Pathol. Oncol. Res.

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“…The human CAF-1 subunit p60 was one of the overexpressed chaperones in CENP-A-overexpressing breast cancer cells [82], and ectopic CENP-A nucleosomes from colorectal cancer cells keep a subpopulation of structurally distinct hybrid (chimeric) nucleosomes containing both CENP-A and H3.3 [82,83]. Misregulation of Scm3/HJURP causes chromosome instability in both yeast and humans [84], and many previous reports suggested the functional relevance of Scm3/HJURP with the development of a wide spectrum of cancers (e.g., colon, lung, liver, breast, pancreatic, brain cancer) [85][86][87][88][89][90][91][92][93][94]. As aforementioned, CAF-1 may cooperate with Psh1 and Scm3 to regulate proteolysis of Cse4, in the way that CAF-1 association with free Cse4 may promote ubiquitylation and proteolysis.…”

Section: Caf-1 Chaperonementioning

confidence: 99%

E3 Ligase for CENP-A (Part 1)

Niikura¹,

Kitagawa²

2022

Hydrolases

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CENP-A is a centromere-specific histone H3 variant that is required to ensure kinetochore assembly for proper chromosome segregation and its function is highly conserved among different species including budding yeast, Saccharomyces cerevisiae. The budding yeast Saccharomyces cerevisiae has genetically defined point centromeres, unlike other eukaryotes. Although, most eukaryotic centromeres are maintained epigenetically, currently only budding yeast S. cerevisiae centromeres are known to be genetically specified by DNA sequence, The small size and sequence specificity of the budding yeast centromere has made yeast a powerful organism for its study in many aspects. Many post-translational modifications (PTMs) of CENP-A and their functions have been recently reported, and studies with budding yeast are providing insights into the role of CENP-A/Cse4 PTMs in kinetochore structure and function. Multiple functions are controlled especially by ubiquitylation and sumoylation by E3 ligases that control CENP-A protein has initially emerged in the budding yeast as an important regulatory mechanism. Here we focus on what is known about the budding yeast E3 ligases for CENP-A/Cse4 ubiquitylation and sumoylation and their biological functions and significance.

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Association between F‐box‐only protein 43 overexpression and hepatocellular carcinoma pathogenesis and prognosis

Qin

Yang

et al. 2023

Cancer Medicine

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Background Despite great advances in the prevention, diagnosis, treatment, and management regarding hepatocellular carcinoma (HCC), the overall prognosis of HCC remains unfavorable. The expression profile, prognostic role, and biological functions of F‐box‐only protein 43 (FBXO43) in HCC remain unclear. Here, we determine the expression profile and prognostic value of FBXO43 in patients with HCC. Materials and Methods A total of 467 HCC patients and their clinicopathological data were collected from the Second Affiliated Hospital of Jiaxing University, the Cancer Genome Atlas (TCGA), and Genotype‐Tissue Expression (GTEx) databases. The expression profile, prognostic value, biological functions, and underlying mechanism of its involvement of FBXO43 were explored based on TCGA, Gene Expression Omnibus (GEO), LinkedOmics, and Cancer Dependency Map (DepMap). The expression of FBXO43 in 93 paired liver tissues was investigated via immunohistochemical staining, tissue microarray analysis, and Western blot. The prognostic value was assessed using survival analysis. Results FBXO43 RNA was upregulated in HCC liver tissues and was associated with an unfavorable prognosis ( p < 0.05). Furthermore, FBXO43 protein was overexpressed in HCC liver tissues compared with that in paired normal liver tissues. Overexpression of FBXO43 protein was significantly associated with advanced TNM stage, large tumor size, lymphatic invasion, distant metastasis, earlier cancer recurrence, and decreased overall survival after radical surgery ( p < 0.05). Cox regression analysis showed that FBXO43 had significant prognostic value in HCC. Importantly, FBXO43 and its co‐expressed genes were mainly involved in cell cycle regulation, DNA replication, metabolic regulation, and so on. FBXO43 knockdown could significantly affect the HCC cell lines growth and proliferation. Conclusions We first revealed that FBXO43 was overexpressed in liver HCC tissues at the RNA and protein levels and served as an independent prognostic factor for HCC patients. Therefore, FBXO43 is worth investigating as a potential HCC treatment target.

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Hypomethylation-driven overexpression of HJURP promotes progression of hepatocellular carcinoma and is associated with poor prognosis

Cited by 15 publications

References 15 publications

Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis

Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis

E3 Ligase for CENP-A (Part 1)

Association between F‐box‐only protein 43 overexpression and hepatocellular carcinoma pathogenesis and prognosis

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