PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma

Wang, Mengyao; Qi, Bin; Wang, Fang; Lin, Zhi-Rui; Li, Mingyi; Yin, Wenwu; Zhu, Yan-Yi; Hé, Lǚ; Yi, Yu; Yang, Fang; Liu, Jinquan; Chen, Dongping

doi:10.1038/s41389-020-00293-9

Cited by 26 publications

(20 citation statements)

References 78 publications

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“…In the correlation analysis of PBK and immune checkpoints, PBK is significantly correlated with VSIR, NRP1, TNFRSF14, LAIR1, CD47, CD200, and CD276. Consistent with recent study, Wang et al (2021) suggested that PBK promotes the CD276 transcription through the enrichment of the MSL complex, which plays an important role in the immune evasion of nasopharyngeal carcinoma (NPC), and may serve as a biomarker for cancer immunotherapy. This suggests that PBK expression might be relevant to the immunotherapy in these immune checkpoints.…”

Section: Discussionsupporting

confidence: 79%

An Integrative Pan-Cancer Analysis of PBK in Human Tumors

Wen

Chen

et al. 2021

Front. Mol. Biosci.

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Background: PDZ binding kinase (PBK) is a serine/threonine kinase, which belongs to the mitogen-activated protein kinase kinase (MAPKK) family. It has been shown to be a critical gene in the regulation of mitosis and tumorigenesis, but the role of PBK in various cancers remains unclear. In this study, we systematically explored the prognostic and predictive value of PBK expression in 33 cancer types.Methods: Public databases including the cBioPortal database, GDSC database, GTEx database, CCLE database, and TCGA database were used to detect the PBK expression and its association with the prognosis, clinicopathologic stage, TMB, MSI, immune microenvironment, immune checkpoints, immune cell infiltration, enrichment pathways, and IC50 across pan-cancer. The statistical analyses and visualization were conducted using R software.Results: PBK expression is relatively high in most cancers compared to their normal counterparts, and this gene is barely expressed in normal tissues. High expression of PBK is significantly associated with poor prognosis and clinicopathologic stages I, II, and III in different cancers. Furthermore, PBK expression is strongly associated with TMB in 23 cancer types and associated with MSI in nine cancer types. Moreover, the correlation analysis of the microenvironment and immune cells indicated that PBK is negatively correlated with the immune infiltration levels but positively correlated with the infiltration levels of M0 and M1 macrophages, T cells CD4 memory activated, and T cells follicular helper. GSEA analysis revealed that the biological function or pathways relevant to the cell cycle and mitosis were frequently enriched at the level of high expression of PBK.Conclusion: These results revealed the oncogenic role of PBK, which is significantly upregulated in various cancers and indicated poor prognosis and immune infiltration in multiple cancers. It also suggested that PBK may serve as a biomarker in multiple tumor progress and patient survival.

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Section: Discussionsupporting

confidence: 79%

An Integrative Pan-Cancer Analysis of PBK in Human Tumors

Wen

Chen

et al. 2021

Front. Mol. Biosci.

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“…PBK expression was positively correlated not only with immune infiltration cells including M2 macrophage, Tregs, CAFs, and MDSCs but also with T-cell exhaustion, which are involved in tumor immune escape [24,34]. Similarly, Wang et al suggested PBK/MSL1/ CD276 signaling axis, which may play an important role in immune evasion of nasopharyngeal carcinoma and may be targeted for cancer immunotherapy [12]. Huang et al identified PBK as one of the 14 hub genes correlated with immune cell infiltration in LIHC [11].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, several recent studies have suggested that PBK/TOPK may be associated with tumor-infiltrating immune cells and have a potential target for cancer immunotherapy [5,11,12]. is study is the first to conduct a pancancer analysis of PBK/TOPK using Oncomine, Human Protein Atlas(HPA), ULCAN, the Tumor Immune Estimation Resource 2.0 (TIMER2.0), STRING, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the data collected from e Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx).…”

Section: Introductionmentioning

confidence: 99%

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

Feng

Zhang

Ling

et al. 2021

Journal of Oncology

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Background. PDZ binding kinase (PBK)/T-LAK cell-derived protein kinase (TOPK) is an important mitotic kinase that promotes tumor progression in some cancers. However, the pan-cancer analysis of PBK/TOPK and its role in tumor immunity are limited. Methods. The oncogenic and immune roles of PBK in various cancers were explored using multiple databases, including Oncomine, Human Protein Atlas, ULCAN, Tumor Immune Estimation Resource 2.0, STRING, and Gene Expression Profiling Interactive Analysis 2, and data collected from The Cancer Genome Atlas and Genotype-Tissue Expression Project. Several bioinformatics tools and methods were used for quantitative analyses and panoramic descriptions, such as the DESeq2 and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Results. PBK was expressed at higher levels in most solid tumors than in normal tissues in multiple databases. PBK was associated with an advanced tumor stage and grade and a poor prognosis in most cases. PBK was associated with tumor immune cell infiltration in most cases and was especially positively correlated with TAMs, Tregs, MDSCs, and T cell exhaustion in KIRC, LGG, and LIHC. PBK was closely related to TMB, MSI, and immune checkpoint genes in various cancers, and patients with higher expression of PBK in KIRC, LGG, and LIHC had higher TIDE scores and lower immune responses in the predicted results. PBK was closely related to cell cycle regulation and immune-related processes in LIHC and LGG according to GO and KEGG enrichment analyses. Conclusions. PBK may play an oncogenic role in most solid tumors and promotes immune escape, especially in KIRC, LGG, and LIHC. This study suggests the potential value of PBK inhibitors combined with immunotherapy.

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“…The up-regulation of CD276 following PBK-overexpression could be reversed by MSL1 depletion. Mechanistically, MSL1 serves as a mediator in the PBK-MSL1-CD276 axis (39). Overall, there are many intertwined factors contributing to the regulation of CD276 expression, which result in the observed relatively low level expression in normal tissue and elevated expression in tumor tissue.…”

Section: Regulatory Mechanisms Of Cd276mentioning

confidence: 99%

The Role of CD276 in Cancers

et al. 2021

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ObjectiveAberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.Data SourcesDatabase including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.ResultsCD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.ConclusionCD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.

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PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma

Cited by 26 publications

References 78 publications

An Integrative Pan-Cancer Analysis of PBK in Human Tumors

An Integrative Pan-Cancer Analysis of PBK in Human Tumors

PDZ Binding Kinase/T-LAK Cell-Derived Protein Kinase Plays an Oncogenic Role and Promotes Immune Escape in Human Tumors

The Role of CD276 in Cancers

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