A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer

Zhang, Chuan; Berndt‐Paetz, Mandy; Neuhaus, Jochen

doi:10.3390/cancers13123089

Cited by 15 publications

(14 citation statements)

References 91 publications

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“…As reported in other studies, compared with control group, DLL4 increased expression of Notch signaling downstream target genes HES1 and HEY2 [14,15] (Figure 4B). Epithelial-to-mesenchymal transition (EMT) is one of major mechanisms for BC metastasis and can be activated by Notch signaling [16]. As previously reported, DLL4 decreased the epithelial marker E-cadherin expression, and increased the mesenchymal marker N-cadherin and Vimentin expression in MDA-MB-231 cells (Figure 4B).…”

Section: Bend5 Blocks Notch Signaling-induced Bc Cell Proliferation M...supporting

confidence: 74%

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling

Shi¹,

Zhang²,

Chen³

et al. 2022

Int. J. Biol. Sci.

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High frequent metastasis is the major cause of breast cancer (BC) mortality among women. However, the molecular mechanisms underlying BC metastasis remain largely unknown. Here, we identified six hub BC metastasis driver genes (BEND5, HSD11B1, NEDD9, SAA2, SH2D2A and TNFSF4) through bioinformatics analysis, among which BEND5 is the most significant gene. Low BEND5 expression predicted advanced stage and shorter overall survival in BC patients. Functional experiments showed that BEND5 could suppress BC growth and metastasis in vitro and in vivo. Mechanistically, BEND5 inhibits Notch signaling via directly interacting with transcription factor RBPJ/CSL. BEN domain of BEND5 interacts with the N-terminal domain (NTD) domain of RBPJ, thus preventing mastermind like transcriptional coactivator (MAML) from forming a transcription activation complex with RBPJ. Our study provides a novel insight into regulatory mechanisms underlying Notch signaling and suggests that BEND5 may become a promising target for BC therapy.

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Section: Bend5 Blocks Notch Signaling-induced Bc Cell Proliferation M...supporting

confidence: 74%

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling

Shi¹,

Zhang²,

Chen³

et al. 2022

Int. J. Biol. Sci.

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“…The present research basically followed many previous research investigating the involvement of a specific group of family genes in a specific cancer type by carrying out bioinformatics analyses [ 27 – 33 ]. The flowchart of the present study was displayed briefly as follows: first, the mutation and expression of NOTCH family genes in TCGA-STAD data were investigated.…”

Section: Methodsmentioning

confidence: 99%

A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma

Xue

Dou

et al. 2021

Disease Markers

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Background. Activation of NOTCH signaling pathways, which are key regulators of multiple cellular functions, has been frequently implicated in cancer pathogenesis, and NOTCH inhibitors have received much recent focus in the context of cancer therapeutics. However, the role and possible involvement of NOTCH pathways in stomach adenocarcinoma (STAD) are unclear. Here, putative regulatory mechanisms and functions of NOTCH pathways in STAD were investigated. Methods. Publicly available data from the TCGA-STAD database were utilized to explore the involvement of canonical NOTCH pathways in STAD by analyzing RNA expression levels of NOTCH receptors, ligands, and downstream genes. Statistical analysis of the data pertaining to cancer and noncancerous samples was performed using R software packages and public databases/webservers. Results. Significant differential gene expression between control and STAD samples was noted for all NOTCH receptors (NOTCH1, 2, 3, and 4), the delta-like NOTCH ligands (DLL-3 and 4), and typical downstream genes (HES1 and HEY1). Four genes (NOTCH1, NOTCH2, NOTCH3, and HEY1) presented prognostic values for the STAD outcome in terms of overall survival. Functional enrichment analysis indicated that NOTCH family genes-strongly correlated genes were mainly enriched in several KEGG signaling pathways such as the PI3K-Akt signaling pathway, human papillomavirus infection, focal adhesion, Rap1 signaling pathway, and ECM-receptor interaction. Gene set enrichment analysis (GSEA) results showed that NOTCH family genes-significantly correlated genes were mainly enriched in four signaling pathways, ECM (extracellular matrix), tumor angiogenesis, inflammatory response, and immune regulation. Conclusions. NOTCH family genes may play an essential role in the progression of STAD by modulating immune cells and mediating ECM synthesis, angiogenesis, focal adhesion, and PI3K-Akt signaling. Multiple NOTCH family genes are valuable candidate biomarkers or therapeutic targets for the management of STAD.

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“…All statistical analyses were performed using R software [ 12 ] . Differences between groups were compared using the Student's t -test.…”

Section: Methodsmentioning

confidence: 99%

Construction of miRNA-mRNA network reveals crucial miRNAs and genes in acute myocardial infarction

Wang¹,

Li²,

Ma³

et al. 2021

J Biomed Res

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Acute myocardial infarction (AMI) is a severe cardiovascular disease. This study aimed to identify crucial microRNAs (miRNAs) and mRNAs in AMI by establishing a miRNA-mRNA network. The microarray datasets GSE31568, GSE148153, and GSE66360 were downloaded from the Gene Expression Omnibus (GEO) database. We identified differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) in AMI samples compared with normal control samples. The consistently changing miRNAs in both GSE31568 and GSE148153 datasets were selected as candidate DE-miRNAs. The interactions between the candidate DE-miRNAs and DE-mRNAs were analyzed, and a miRNA-mRNA network and a protein-protein interaction network were constructed, along with functional enrichment and pathway analyses. A total of 209 DE-miRNAs in the GSE31568 dataset, 857 DE-miRNAs in the GSE148153 dataset, and 351 DE-mRNAs in the GSE66360 dataset were identified. Eighteen candidate DE-miRNAs were selected from both the GSE31568 and GSE148153 datasets. Furthermore, miR-646 , miR-127-5p , miR-509-5p , miR-509-3-5p , and miR-767-5p were shown to have a higher degree in the miRNA-mRNA network. THBS-1 as well as FOS was a hub gene in the miRNA-mRNA network and the protein-protein interaction (PPI) network, respectively. CDKN1A was important in both miRNA-mRNA network and PPI network. We established a miRNA-mRNA network in AMI and identified five miRNAs and three genes, which might be used as biomarkers and potential therapeutic targets for patients with AMI.

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A Comprehensive Bioinformatics Analysis of Notch Pathways in Bladder Cancer

Cited by 15 publications

References 91 publications

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling

A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma

Construction of miRNA-mRNA network reveals crucial miRNAs and genes in acute myocardial infarction

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