WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer

Li, Zijian; Feng, Min; Zhang, Jie; Wang, Xingzhou; Xu, En; Wang, Chao; Lin, Fengcen; Yang, Zhi; Heng, Yu; Guan, Wenxian; Wang, Hao

doi:10.1186/s12935-021-02109-1

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…NOTUM, one of the Wnt target genes, was found to be up-regulated in clinical specimens of colon cancer 40 . Similarly, immunohistochemistry detection confirmed WDR43 overexpression in CRC patient specimens 41 . What’s more, several studies have reported the oncogenic role of TRIB3 in CRC 42 .…”

Section: Discussionmentioning

confidence: 61%

Identification of gene signatures for COAD using feature selection and Bayesian network approaches

Wang

Gao²,

Ru³

et al. 2022

Sci Rep

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The combination of TCGA and GTEx databases will provide more comprehensive information for characterizing the human genome in health and disease, especially for underlying the cancer genetic alterations. Here we analyzed the gene expression profile of COAD in both tumor samples from TCGA and normal colon tissues from GTEx. Using the SNR-PPFS feature selection algorithms, we discovered a 38 gene signatures that performed well in distinguishing COAD tumors from normal samples. Bayesian network of the 38 genes revealed that DEGs with similar expression patterns or functions interacted more closely. We identified 14 up-DEGs that were significantly correlated with tumor stages. Cox regression analysis demonstrated that tumor stage, STMN4 and FAM135B dysregulation were independent prognostic factors for COAD survival outcomes. Overall, this study indicates that using feature selection approaches to select key gene signatures from high-dimensional datasets can be an effective way for studying cancer genomic characteristics.

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Section: Discussionmentioning

confidence: 61%

Identification of gene signatures for COAD using feature selection and Bayesian network approaches

Wang

Gao²,

Ru³

et al. 2022

Sci Rep

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“…Dysregulation of protein synthesis and degradation pathways, including the ubiquitin-proteasome system and autophagy-lysosome pathway, has been implicated in the pathogenesis of PD, and previous research has suggested that WDR43 may play a role in ribosome biogenesis and protein synthesis. In addition, WDR43 has been implicated in the development of human estrogen receptor-negative breast cancer and identified as a possible therapeutic target for colorectal cancer ( Couch et al, 2016 ; Bi et al, 2019 ; Li et al, 2021 ; Sun et al, 2022 ). Furthermore, WDR43 and NOL11 are required to form a protein complex to ensure successful segregation of chromosomes at kinetochores and centromeres ( Shibamura et al, 2004 ; Fujimura et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43

Wang

Kong

Lin

2023

Front. Aging Neurosci.

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BackgroundCerebral vasospasm (CV) can cause inflammation and damage to neuronal cells in the elderly, leading to dementia.PurposeThis study aimed to investigate the genetic mechanisms underlying dementia caused by CV in the elderly, identify preventive and therapeutic drugs, and evaluate their efficacy in treating neurodegenerative diseases.MethodsGenes associated with subarachnoid hemorrhage and CV were acquired and screened for differentially expressed miRNAs (DEmiRNAs) associated with aneurysm rupture. A regulatory network of DEmiRNAs and mRNAs was constructed, and virtual screening was performed to evaluate possible binding patterns between Food and Drug Administration (FDA)-approved drugs and core proteins. Molecular dynamics simulations were performed on the optimal docked complexes. Optimally docked drugs were evaluated for efficacy in the treatment of neurodegenerative diseases through cellular experiments.ResultsThe study found upregulated genes (including WDR43 and THBS1) and one downregulated gene associated with aneurysm rupture. Differences in the expression of these genes indicate greater disease risk. DEmiRNAs associated with ruptured aortic aneurysm were identified, of which two could bind to THBS1 and WDR43. Cromolyn and lanoxin formed the best docking complexes with WDR43 and THBS1, respectively. Cellular experiments showed that cromolyn improved BV2 cell viability and enhanced Aβ42 uptake, suggesting its potential as a therapeutic agent for inflammation-related disorders.ConclusionThe findings suggest that WDR43 and THBS1 are potential targets for preventing and treating CV-induced dementia in the elderly. Cromolyn may have therapeutic value in the treatment of Alzheimer’s disease and dementia.

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“…Intriguingly, several bioinformatics analysis identified WDR43 as a crucial oncogene contributing to the development of colorectal/lung cancer via promoting the migration and proliferation of cancer cells through GEO and The Cancer Genome Atlas (TCGA) database. Mechanistically, c-MYC/WDR43/MDM2 mediated p53 degradation, and cyclin-dependent kinase 2 were involved in the underlyng mechanism [ 34 – 36 ]. However, the role of WDR43 in PAH remains uninvestigated..…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes based on integrated analysis of single-cell and microarray transcriptome in patients with pulmonary arterial hypertension

Qin,

Yan,

Qiao

et al. 2023

BMC Genomics

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Background Pulmonary arterial hypertension (PAH) is a devastating chronic cardiopulmonary disease without an effective therapeutic approach. The underlying molecular mechanism of PAH remains largely unexplored at single-cell resolution. Methods Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database (GSE210248) was included and analyzed comprehensively. Additionally, microarray transcriptome data including 15 lung tissue from PAH patients and 11 normal samples (GSE113439) was also obtained. Seurat R package was applied to process scRNA-seq data. Uniform manifold approximation and projection (UMAP) was utilized for dimensionality reduction and cluster identification, and the SingleR package was performed for cell annotation. FindAllMarkers analysis and ClusterProfiler package were applied to identify differentially expressed genes (DEGs) for each cluster in GSE210248 and GSE113439, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) were used for functional enrichment analysis of DEGs. Microenvironment Cell Populations counter (MCP counter) was applied to evaluate the immune cell infiltration. STRING was used to construct a protein-protein interaction (PPI) network of DEGs, followed by hub genes selection through Cytoscape software and Veen Diagram. Results Nineteen thousand five hundred seventy-six cells from 3 donors and 21,896 cells from 3 PAH patients remained for subsequent analysis after filtration. A total of 42 cell clusters were identified through UMAP and annotated by the SingleR package. 10 cell clusters with the top 10 cell amounts were selected for consequent analysis. Compared with the control group, the proportion of adipocytes and fibroblasts was significantly reduced, while CD8+ T cells and macrophages were notably increased in the PAH group. MCP counter revealed decreased distribution of CD8+ T cells, cytotoxic lymphocytes, and NK cells, as well as increased infiltration of monocytic lineage in PAH lung samples. Among 997 DEGs in GSE113439, module 1 with 68 critical genes was screened out through the MCODE plug-in in Cytoscape software. The top 20 DEGs in each cluster of GSE210248 were filtered out by the Cytohubba plug-in using the MCC method. Eventually, WDR43 and GNL2 were found significantly increased in PAH and identified as the hub genes after overlapping these DEGs from GSE210248 and GSE113439. Conclusion WDR43 and GNL2 might provide novel insight into revealing the new molecular mechanisms and potential therapeutic targets for PAH.

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WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer

Cited by 12 publications

References 24 publications

Identification of gene signatures for COAD using feature selection and Bayesian network approaches

Identification of gene signatures for COAD using feature selection and Bayesian network approaches

Cromolyn prevents cerebral vasospasm and dementia by targeting WDR43

Identification of hub genes based on integrated analysis of single-cell and microarray transcriptome in patients with pulmonary arterial hypertension

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