AZGP1 is androgen responsive and involved in AR‐induced prostate cancer cell proliferation and metastasis

Cao, Runyi; Ke, Manzhu; Wu, Qingxin; Tian, Qian; Liu, Li; Dai, Zao; Lu, Shan; Liu, Ping

doi:10.1002/jcp.28366

Cited by 27 publications

(28 citation statements)

References 48 publications

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“…Six genes were incorporated into this model, consisting of AZGP1, IGF2BP2, MEX3A, NUDT16, NUP153, and USB1. A recent research proved that AZGP1 is an AR target gene and is involved in androgen/AR axis-mediated cell proliferation and metastasis in primary PCa ( 28 ). Meanwhile the six-gene model revealed that high expression of AZGP1 was negatively associated with prognosis in thyroid cancer, so it might also play a critical role in thyroid cancer.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Functions and Prognostic Value of RNA-Binding Proteins in Thyroid Cancer

Yin

Liu

et al. 2021

Front. Oncol.

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RNA binding proteins (RBPs) have been proved to play pivotal roles in a variety types of tumors. However, there is no convincible evidence disclosing the functions of RBPs in thyroid cancer (THCA) thoroughly and systematically. Integrated analysis of the functional and prognostic effect of RBPs help better understanding tumorigenesis and development in thyroid and may provide a novel therapeutic method for THCA. In this study, we obtained a list of human RBPs from Gerstberger database, which covered 1,542 genes encoding RBPs. Gene expression data of THCA was downloaded from The Cancer Genome Atlas (TCGA, n = 567), from which we extracted 1,491 RBPs’ gene expression data. We analyzed differentially expressed RBPs using R package “limma”. Based on differentially expressed RBPs, we constructed protein-protein interaction network and the GO and KEGG pathway enrichment analyses were carried out. We found six RBPs (AZGP1, IGF2BP2, MEX3A, NUDT16, NUP153, USB1) independently associated with prognosis of patients with thyroid cancer according to univariate and multivariate Cox proportional hazards regression models. The survival analysis and risk score analysis achieved good performances from this six-gene prognostic model. Nomogram was constructed to guide clinical decision in practice. Finally, biological experiments disclosed that NUP153 and USB1 can significantly impact cancer cell proliferation and migration. In conclusion, our research provided a new insight of thyroid tumorigenesis and development based on analyses of RBPs. More importantly, the six-gene model may play an important role in clinical practice in the future.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Functions and Prognostic Value of RNA-Binding Proteins in Thyroid Cancer

Yin

Liu

et al. 2021

Front. Oncol.

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“…A recent report demonstrated involvement of the AR target gene—alpha-2-glycoprotein 1, zinc-binding ( AZGP1 )—in induction of PCa proliferation and metastasis. The authors revealed that AR signaling was responsible for upregulation of AZGP1 and enhancement of cell proliferation in vitro and in vivo through the androgen/AR axis [92].…”

Section: Androgen Receptor (Ar) and Pcamentioning

confidence: 99%

ZBTB46, SPDEF, and ETV6: Novel Potential Biomarkers and Therapeutic Targets in Castration-Resistant Prostate Cancer

Fararjeh

Liu

2019

IJMS

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Prostate cancer (PCa) is the second most common killer among men in Western countries. Targeting androgen receptor (AR) signaling by androgen deprivation therapy (ADT) is the current therapeutic regime for patients newly diagnosed with metastatic PCa. However, most patients relapse and become resistant to ADT, leading to metastatic castration-resistant PCa (CRPC) and eventually death. Several proposed mechanisms have been proposed for CRPC; however, the exact mechanism through which CRPC develops is still unclear. One possible pathway is that the AR remains active in CRPC cases. Therefore, understanding AR signaling networks as primary PCa changes into metastatic CRPC is key to developing future biomarkers and therapeutic strategies for PCa and CRPC. In the current review, we focused on three novel biomarkers (ZBTB46, SPDEF, and ETV6) that were demonstrated to play critical roles in CRPC progression, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) drug resistance, and the epithelial-to-mesenchymal transition (EMT) for patients treated with ADT or AR inhibition. In addition, we summarize how these potential biomarkers can be used in the clinic for diagnosis and as therapeutic targets of PCa.

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“…Analyses of the Hallmark gene sets revealed androgen response genes were negatively and peroxisome genes positively enriched, respectively, suggesting that PGC1α expression represses AR signaling and enhances the activity of the peroxisome. AR target genes notably associated with energy production were repressed, including the putative tumor suppressor hydroxyprostaglandin dehydrogenase ( HPGD ) 75 , as well as Acyl-CoA synthetase long chain family member 3 (ACSL3) 76 and Alpha-2-glycoprotein 1, zinc-binding ( AZGP1 ) 77 . Up-regulated peroxisome genes included retinoic acid anabolizing enzyme, Dehydrogenase/Reductase 3 ( DHRS3 ) 78 , and the steroid catabolizing enzyme UDP Glucuronosyltransferase Family 2 Member B17 ( UGT2B17 ) 79 .…”

Section: Resultsmentioning

confidence: 99%

Identification of transcription factor co-regulators that drive prostate cancer progression

Siddappa

Wani

Long

et al. 2020

Sci Rep

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In prostate cancer (PCa), and many other hormone-dependent cancers, there is clear evidence for distorted transcriptional control as disease driver mechanisms. Defining which transcription factor (TF) and coregulators are altered and combine to become oncogenic drivers remains a challenge, in part because of the multitude of TFs and coregulators and the diverse genomic space on which they function. The current study was undertaken to identify which TFs and coregulators are commonly altered in PCa. We generated unique lists of TFs (n = 2662), coactivators (COA; n = 766); corepressors (COR; n = 599); mixed function coregulators (MIXED; n = 511), and to address the challenge of defining how these genes are altered we tested how expression, copy number alterations and mutation status varied across seven prostate cancer (PCa) cohorts (three of localized and four advanced disease). Testing of significant changes was undertaken by bootstrapping approaches and the most significant changes were identified. For one commonly and significantly altered gene were stably knocked-down expression and undertook cell biology experiments and RNA-Seq to identify differentially altered gene networks and their association with PCa progression risks. COAS, CORS, MIXED and TFs all displayed significant down-regulated expression (q.value < 0.1) and correlated with protein expression (r 0.4–0.55). In localized PCa, stringent expression filtering identified commonly altered TFs and coregulator genes, including well-established (e.g. ERG) and underexplored (e.g. PPARGC1A, encodes PGC1α). Reduced PPARGC1A expression significantly associated with worse disease-free survival in two cohorts of localized PCa. Stable PGC1α knockdown in LNCaP cells increased growth rates and invasiveness and RNA-Seq revealed a profound basal impact on gene expression (~ 2300 genes; FDR < 0.05, logFC > 1.5), but only modestly impacted PPARγ responses. GSEA analyses of the PGC1α transcriptome revealed that it significantly altered the AR-dependent transcriptome, and was enriched for epigenetic modifiers. PGC1α-dependent genes were overlapped with PGC1α-ChIP-Seq genes and significantly associated in TCGA with higher grade tumors and worse disease-free survival. These methods and data demonstrate an approach to identify cancer-driver coregulators in cancer, and that PGC1α expression is clinically significant yet underexplored coregulator in aggressive early stage PCa.

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AZGP1 is androgen responsive and involved in AR‐induced prostate cancer cell proliferation and metastasis

Cited by 27 publications

References 48 publications

Comprehensive Analysis of the Functions and Prognostic Value of RNA-Binding Proteins in Thyroid Cancer

Comprehensive Analysis of the Functions and Prognostic Value of RNA-Binding Proteins in Thyroid Cancer

ZBTB46, SPDEF, and ETV6: Novel Potential Biomarkers and Therapeutic Targets in Castration-Resistant Prostate Cancer

Identification of transcription factor co-regulators that drive prostate cancer progression

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