HJURP regulates cell proliferation and chemo-resistance via YAP1/NDRG1 transcriptional axis in triple-negative breast cancer

Mao, Misha; Jia, Yunlu; Chen, Yongxia; Yang, Jingjing; Xu, Ling; Zhang, Xun; Zhou, Jichun; Li, Zhaoqing; Chen, Cong; Ju, Siwei; Wang, Linbo

doi:10.1038/s41419-022-04833-6

Cited by 25 publications

(19 citation statements)

References 30 publications

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“…Indeed, our study identifies several aspects of HJURP that deserve further study, including the downstream effector molecules that mediate the observed associations between HJURP and HCC pathogenesis. HJURP has already been shown to regulate pathways involving GSK3β/JNK, p53, Wnt/ β-catenin, MDM2/p53, YAP1/NDRG1, MAPK/ERK1/2, AKT/ GSK3β, and SPHK1 (11)(12)(13)(14)(35)(36)(37). Among these pathways, those involving MAPK/ERK1/2 and AKT/GSK3β have been associated with HCC proliferation (13), while SPHK1 signaling has been associated with the epithelial-to-mesenchymal transition in HCC (37).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…We also noticed this inconsistency in HJURP sub-localization in previous studies. In hepatocellular carcinoma, prostate cancer, ovarian cancer, and breast cancer, IHC showed that HJURP was mainly expressed in cell cytoplasm ( 16 , 21 – 24 ); nevertheless, HJURP was mainly observed in cytoplasm in pancreatic cancer and colorectal cancer ( 15 , 17 ). The underlying mechanism of this expression phenotype is still unknown.…”

Section: Discussionmentioning

confidence: 99%

The expression, clinical relevance, and prognostic significance of HJURP in cholangiocarcinoma

Yang

Yuan²,

Liu³

et al. 2022

Front. Oncol.

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BackgroundCholangiocarcinoma (CCA) is the malignancy originating from the biliary epithelium, including intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) CCA. The prognosis of CCA is very poor, and the biomarkers of different CCA subsets should be investigated separately. Holliday junction recognition protein (HJURP) is a key component of the pre-nucleosomal complex, which is responsible for normal mitosis. The ectopic expression of HJURP has been reported in several cancers, but not CCA.Materials and methodsIn our study, we investigated the expression of HJURP in 127 CCA patients which were composed of 32 iCCAs, 71 pCCAs, and 24 dCCAs with immunohistochemistry and divided these patients into subgroups with a low or high expression of HJURP. With chi-square test and univariate and multivariate analyses, we evaluated the clinical relevance and prognostic significance of HJURP in iCCAs, pCCAs, and dCCAs.ResultsHJURP was ectopically upregulated in CCAs compared with the para-tumor tissues based on TCGA and other mRNA-seq databases. A high expression of HJURP was correlated with low overall survival rates of iCCA and pCCA, but not in dCCA. Moreover, HJURP was an independent prognostic biomarker in both iCCA and pCCA. Patients with high HJURP were more likely to suffer CCA-related death after operation.ConclusionsHJURP was an independent prognostic biomarker in both iCCA and pCCA, but not in dCCA. Our results provide more evidence of the molecular features of different CCA subsets and suggest that patients with high HJURP are more high-risk, which can guide more precision follow-up and treatment of CCA.

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“…Simultaneously inhibiting YAP activity can improve the therapeutic effect of liver cancer patients with drug resistance mechanism [45] . In breast cancer, YAP1 also can affect chemotherapy sensitivity through the HJURP/YAP1/NDRG1 axis [46] . However, there is still no research on the drug resistance mechanism of YAP1 in LCNEC, so the underlying mechanism of drug resistance induced by YAP1 still remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of YAP1 expression and its association with neuroendocrine markers in resected pulmonary large cell neuroendocrine carcinoma (LCNEC)

Sun¹,

Zhang²,

Dong³

et al. 2022

Translational Oncology

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HJURP regulates cell proliferation and chemo-resistance via YAP1/NDRG1 transcriptional axis in triple-negative breast cancer

Cited by 25 publications

References 30 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

The expression, clinical relevance, and prognostic significance of HJURP in cholangiocarcinoma

Prognostic significance of YAP1 expression and its association with neuroendocrine markers in resected pulmonary large cell neuroendocrine carcinoma (LCNEC)

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