ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21

Deng, Minhua; Wei, Wensu; Duan, Jin‐Ling; Chen, Rixin; Wang, Ning; He, Leye; Peng, Yulu; Ma, Xiaodan; Zg, Wu; Liu, Jianye; Li, Zhiyong; Zhang, Zhiling; Jiang, Lijuan; Zhou, Fangjian; Xie, Dan

doi:10.1111/cas.14810

Cited by 23 publications

(23 citation statements)

References 37 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two signature genes (ZHX3 and SUZ12) were positively correlated with the occurrence of BC, while a negative correlation was instead determined for the remaining 5 genes (ZNF350, ZNRD1, ZNF195, APEX2, and EBF4). In line with a recent study [ 18 ], our results showed that ZHX3 plays an oncogenic role in BC pathogenesis. Interestingly, ZHX3 has also shown to act as a tumor suppressor in renal cell carcinoma [ 19 ], breast cancer [ 20 ], and liver cancer [ 21 ].…”

Section: Discussionsupporting

confidence: 93%

A zinc finger protein gene signature enables bladder cancer treatment stratification

Zhang

Cao

et al. 2021

Aging

View full text Add to dashboard Cite

Bladder cancer (BC) is a commonly occurring malignant tumor affecting the urinary tract. Zinc finger proteins (ZNFs) constitute the largest transcription factor family in the human genome and are therefore attractive biomarker candidates for BC prognosis. In this study, we profiled the expression of ZNFs in The Cancer Genome Atlas (TCGA) BC cohort and developed a novel prognostic signature based on 7 ZNF-coding genes. After external validation of the model in the GSE48276 dataset, we integrated the 7-ZNF-gene signature with patient clinicopathological data to construct a nomogram that forecasted 1-, 2-, and 3-year OS with good predictive accuracy. We then accessed The Genomics of Drug Sensitivity in Cancer database to predict the therapeutic drug responses of signature-defined high- and low-risk BC patients in the TCGA cohort. Greater sensitivity to chemotherapy was revealed in the low-risk group. Finally, we conducted gene set enrichment analysis of the signature genes and established, by applying the ESTIMATE algorithm, distinct correlations between the two risk groups and the presence of stromal and immune cell types in the tumor microenvironment. By allowing effective risk stratification of BC patients, our novel ZNF gene signature may enable tailoring more intensive treatment for high-risk patients.

show abstract

Section: Discussionsupporting

confidence: 93%

A zinc finger protein gene signature enables bladder cancer treatment stratification

Zhang

Cao

et al. 2021

Aging

View full text Add to dashboard Cite

show abstract

“…Together, this suggests that both AR-mediated effects in cell migration and colony formation in UM-UC-3-AR are tightly linked. With these phenotypic changes, several genes were significantly upregulated upon hormone stimulation, among which some previously described for their role in promoting migration and colony formation of diverse type of cancer models such as FKBP5, LDH-A, GREB1, PDLIM1, TNK2, VASP, ARHGAP31 and ZHX3 [40][41][42][43][44][45][46][47], and genes known to drive the development of cancer cells with stem cell-like characteristics such as TFCP2L1 and SH3RF3 [48,49]. These genes were consistently downregulated upon treatment with enzalutamide or after AR knockdown, which validates them as androgen-responsive genes.…”

Section: Discussionmentioning

confidence: 92%

Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder

et al. 2021

View full text Add to dashboard Cite

Bladder urothelial cell carcinoma (UCC) incidence is about three times higher in men compared with women. There are several indications for the involvement of hormonal factors in the aetiology of UCC. Here, we provide evidence of androgen signalling in UCC progression. Microarray and qPCR analysis revealed that the androgen receptor (AR) mRNA level is upregulated in a subset of UCC cases. In an AR‐positive UCC‐derived cell line model, UM‐UC‐3‐AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell‐like holoclones, while AR knockdown or treatment with the AR antagonist enzalutamide abrogated this clonogenic advantage. Additionally, blockage of AR signalling reduced the cell migration potential of androgen‐stimulated UM‐UC‐3‐AR cells. These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.

show abstract

“…Our study is the first research that identified the risk of RGS19 on BLCA by means of bioinformatic analysis in combination with experiment. In addition, we found a potential therapeutic drug, GSK1070916, for BLCA patients with high expression of RGS19 [31][32][33][34].…”

Section: Discussionmentioning

confidence: 93%

Genome-wide screening for the G-protein-coupled receptor (GPCR) pathway-related therapeutic gene RGS19 (regulator of G protein signaling 19) in bladder cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

ZHX3 promotes the progression of urothelial carcinoma of the bladder via repressing of RGS2 and is a novel substrate of TRIM21

Cited by 23 publications

References 37 publications

A zinc finger protein gene signature enables bladder cancer treatment stratification

A zinc finger protein gene signature enables bladder cancer treatment stratification

Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder

Genome-wide screening for the G-protein-coupled receptor (GPCR) pathway-related therapeutic gene RGS19 (regulator of G protein signaling 19) in bladder cancer

Contact Info

Product

Resources

About