CEP55 Inhibitor: Extensive Computational Approach Defining a New Target of Cell Cycle Machinery Agent

Lestari, Beni; Utomo, Rohmad Yudi

doi:10.34172/apb.2022.021

Cited by 4 publications

(4 citation statements)

References 33 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CEP55 is a key protein involved in cytokinesis during cell division and is specifically expressed in testis and various types of cancers but not in normal cells [51][52][53]. It has been proposed as a candidate for peptide vaccine therapy in cancers like colorectal carcinoma and breast carcinoma [52,54,55].…”

Section: Discussionmentioning

confidence: 99%

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Wang,

Mao,

Zhang

et al. 2024

Kidney Blood Press Res

View full text Add to dashboard Cite

Introduction: Accumulating evidence has disclosed that IgA nephropathy (IgAN) could present shortly after the second dose of COVID-19 mRNA vaccine. However, the undying mechanism remains unclear and we aimed to investigate the potential molecular mechanisms. Methods: We downloaded gene expression datasets of COVID-19 mRNA vaccination (GSE201535) and IgAN (GSE104948). Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify co-expression modules related to the second dose of COVID-19 mRNA vaccination and IgAN. Differentially expressed genes (DEGs) were screened, and a transcription factor (TF)-miRNA regulatory network and protein-drug interaction were constructed for the shared genes. Results: WGCNA identified one module associated with the second dose of COVID-19 mRNA vaccine and four modules associated with IgAN. Gene Ontology (GO) analyses revealed enrichment of cell cycle-related processes for the COVID-19 mRNA vaccine hub genes and immune effector processes for the IgAN hub genes. We identified 74 DEGs for the second dose of COVID-19 mRNA vaccine and 574 DEGs for IgAN. Intersection analysis with COVID-19 vaccine-related genes led to the identification of two shared genes, TOP2A and CEP55. The TF-miRNA network analysis showed that hsa-miR-144 and ATF1 might regulate the shared hub genes. Conclusions: This study provides insights into the common pathogenesis of COVID-19 mRNA vaccination and IgAN. The identified pivotal genes may offer new directions for further mechanistic studies of IgAN secondary to COVID-19 mRNA vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Wang,

Mao,

Zhang

et al. 2024

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…Previous studies already identified CEP55 as potential target for anticancer therapies. Although, no specific small molecule inhibitors against CEP55 exist to our knowledge, first computational approaches for the design of future drugs have been performed [ 58 ]. However, alternative approaches targeting upstream regulatory mechanisms of CEP55 may also present possible strategies to block its tumor-supporting properties.…”

Section: Discussionmentioning

confidence: 99%

α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration

et al. 2023

View full text Add to dashboard Cite

Background Adherens junctions (AJs) facilitate cell–cell contact and contribute to cellular communication as well as signaling under physiological and pathological conditions. Aberrant expression of AJ proteins is frequently observed in human cancers; however, how these factors contribute to tumorigenesis is poorly understood. In addition, for some factors such as α‐catenin contradicting data has been described. In this study we aim to decipher how the AJ constituent α‐catenin contributes to liver cancer formation. Methods TCGA data was used to detect transcript changes in 23 human tumor types. For the detection of proteins, liver cancer tissue microarrays were analyzed by immunohistochemistry. Liver cancer cell lines (HLF, Hep3B, HepG2) were used for viability, proliferation, and migration analyses after RNAinterference-mediated gene silencing. To investigate the tumor initiating potential, vectors coding for α‐catenin and myristoylated AKT were injected in mice by hydrodynamic gene delivery. A BioID assay combined with mass spectrometry was performed to identify α‐catenin binding partners. Results were confirmed by proximity ligation and co-immunoprecipitation assays. Binding of transcriptional regulators at gene promoters was investigated using chromatin-immunoprecipitation. Results α‐catenin mRNA was significantly reduced in many human malignancies (e.g., colon adenocarcinoma). In contrast, elevated α‐catenin expression in other cancer entities was associated with poor clinical outcome (e.g., for hepatocellular carcinoma; HCC). In HCC cells, α‐catenin was detectable at the membrane as well as cytoplasm where it supported tumor cell proliferation and migration. In vivo, α‐catenin facilitated moderate oncogenic properties in conjunction with AKT overexpression. Cytokinesis regulator centrosomal protein 55 (CEP55) was identified as a novel α‐catenin-binding protein in the cytoplasm of HCC cells. The physical interaction between α‐catenin and CEP55 was associated with CEP55 stabilization. CEP55 was highly expressed in human HCC tissues and its overexpression correlated with poor overall survival and cancer recurrence. Next to the α‐catenin-dependent protein stabilization, CEP55 was transcriptionally induced by a complex consisting of TEA domain transcription factors (TEADs), forkhead box M1 (FoxM1), and yes-associated protein (YAP). Surprisingly, CEP55 did not affect HCC cell proliferation but significantly supported migration in conjunction with α‐catenin. Conclusion Migration-supporting CEP55 is induced by two independent mechanisms in HCC cells: stabilization through interaction with the AJ protein α‐catenin and transcriptional activation via the FoxM1/TEAD/YAP complex.

show abstract

“…Over the past decades, this has been the most common method of new drug discovery and has given birth to a number of batches of antitumor drugs entering clinical studies [60][61][62]. Given the role of CEP55, we refined and screened potential compounds as new therapeutic strategies [63]. Our analysis from the RNAactDrug and cMap databases revealed that compounds including AZD7762, bleomycin, midostaurin, afatinib, and tanespimycin significantly reduced CEP55 mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

CEP55 as a Promising Immune Intervention Marker to Regulate Tumor Progression: A Pan-Cancer Analysis with Experimental Verification

Wang,

Chen,

et al. 2023

Cells

View full text Add to dashboard Cite

CEP55, a member of the centrosomal protein family, affects cell mitosis and promotes the progression of several malignancies. However, the relationship between CEP55 expression levels and prognosis, as well as their role in cancer progression and immune infiltration in different cancer types, remains unclear. We used a combined form of several databases to validate the expression of CEP55 in pan-cancer and its association with immune infiltration, and we further screened its targeted inhibitors with CEP55. Our results showed the expression of CEP55 was significantly higher in most tumors than in the corresponding normal tissues, and it correlated with the pathological grade and age of the patients and affected the prognosis. In breast cancer cells, CEP55 knockdown significantly decreased cell survival, proliferation, and migration, while overexpression of CEP55 significantly promoted breast cancer cell proliferation and migration. Moreover, CEP55 expression was positively correlated with immune cell infiltration, immune checkpoints, and immune-related genes in the tumor microenvironment. CD-437 was screened as a potential CEP55-targeted small-molecule compound inhibitor. In conclusion, our study highlights the prognostic value of CEP55 in cancer and further provides a potential target selection for CEP55 as a potential target for intervention in tumor immune infiltration and related immune genes.

show abstract

CEP55 Inhibitor: Extensive Computational Approach Defining a New Target of Cell Cycle Machinery Agent

Cited by 4 publications

References 33 publications

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

Molecular Pathogenic Mechanisms of IgA Nephropathy Secondary to COVID-19 mRNA Vaccination

α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration

CEP55 as a Promising Immune Intervention Marker to Regulate Tumor Progression: A Pan-Cancer Analysis with Experimental Verification

Contact Info

Product

Resources

About