Silencing TAK1 alters gene expression signatures in bladder cancer cells

Abstract

Abstract. The aim of the present study was to identify the differentially expressed genes (DEGs) that are induced by the silencing of transforming growth factor-β-activated kinase 1 (TAK1) in bladder cancer cells and to analyze the potential biological effects. Dataset GSE52452 from mutant fibroblast growth factor receptor 3 (FGFR3) bladder cancer cells transfected with control siRNA or TAK1-specific siRNA was downloaded from Gene Expression Omnibus. The DEGs between the two groups were identified using Limma package following data pre-processing by Affy in Bioconductor. Enrichment analysis of DEGs was performed using the Database for Annotation, Visualization and Integrated Discovery, followed by functional annotation using TRANSFAC, TSGene and TAG databases. Integrated networks were constructed by Cytoscape and sub-networks were extracted employing BioNet, followed by enrichment analysis of DEGs in the sub-network. A total of 43 downregulated and 21 upregulated genes were obtained. The downregulated genes were enriched in five pathways, including NOD-like receptor signaling pathway and functions related to cellular response. The upregulated genes were associated with cellular developmental processes. Transcription factor EGR1 and 9 tumor-associated genes were screened from the DEGs. Among the DEGs, 10 hub nodes may represent important roles in the complex metabolic network, including EGFR, CYP3A5, MAP3K7, GSTA1, PTHLH, ALDH1A1, KCND2, EGR1, ARRB1 and ITPR1. Additionally, EGFR was correlated with ERBB2, GRB2 and PIK3R1, and these were enriched in ErbB signaling pathway and various cancer-associated pathways. Silencing TAK1 may decrease cellular response to chemical stimulus via downregulating CYP3A5, MAP3K7, GSTA1, ALDH1A1, ARRB1 and ITPR1; increase cancer cell development via upregulating EGFR, EGR1 and PTHLH; and regulate cancer metastasis through EGFR, ERBB2, GRB2 and PIK3R1.

Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa‐miR‐23b‐3p/KCND2 axis

“…There are some studies reported their involvement in cancer biology. For example, KCND2 upregulation was associated with cancer stem cell properties of neuroblastoma cells, 35 KCND2 was also considered as a hub gene in the complex metabolic network of bladder cancer 36 . One recent study found that KCND2 upregulation was a valuable prognostic biomarker in gastric cancer patients 37 .…”

A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer

“…PTHLH functions as a critical regulator of cellular and organ growth, development, migration, survival and of epithelial calcium ion transport (45). Recently, Chen et al revealed that silencing of transforming growth factor-b-activated kinase 1 (TAK1) in BC cells promote the development of cancer cells by upregulating PTHLH (46). CTSE is involved in antigen processing and the maturation of secretory proteins, which can regulate the processing of antigenic peptides during MHC class II-mediated antigen presentation.…”

Identifying a panel of genes/proteins/miRNAs modulated by arsenicals in bladder, prostate, kidney cancers

“…However, it is important to underline that arsenite trioxide has been reported to induce the phosphorylation of RXRA, subsequent to oxidative damages and the activation of the stress-activated protein kinases cascade 48 . MAP3K7 was reported to be down-regulated in BlC and PrC 49 . NR3C1 resulted to be down-regulated in KiC as well as in BlC 50 , 51 and its NR3C1 polymorphism was associated to PrC risk 52 .…”