Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression

Goel, Sakshi; Bhatia, Vipul; Kundu, Sushmita; Biswas, Tanay; Carskadon, Shannon; Gupta, Nilesh; Asim, Mohammad; Morrissey, Colm; Palanisamy, Nallasivam; Ateeq, Bushra

doi:10.1038/s41467-021-25623-2

Cited by 28 publications

(14 citation statements)

References 80 publications

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“…HOXC6 expression is upregulated in localized, advanced, and metastatic PCa, promoting proliferation [30]. As an androgen-independent AR co-factor, HOXC6 can drive noncanonical AR signaling under castrate conditions and theoretically promote DLX1 expression in ERG-negative mCRPC [30][31][32]. This could ex-plain their consistent prognostic utility in both CTC and urinary liquid biopsy studies [33].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling of Circulating Tumor Cells to Predict Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer

Groen

Kloots

Englert

et al. 2023

IJMS

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The clinical utility of circulating tumor cells (CTC) as a non-invasive multipurpose biomarker is broadly recognized. The earliest methods for enriching CTCs from whole blood rely on antibody-based positive selection. The prognostic utility of CTC enumeration using positive selection with the FDA-approved CellSearchTM system has been demonstrated in numerous studies. The capture of cells with specific protein phenotypes does not fully represent cancer heterogeneity and therefore does not realize the prognostic potential of CTC liquid biopsies. To avoid this selection bias, CTC enrichment based on size and deformability may provide better fidelity, i.e., facilitate the characterization of CTCs with any phenotype. In this study, the recently FDA-approved Parsortix® technology was used to enrich CTCs from prostate cancer (PCa) patients for transcriptome analysis using HyCEADTM technology. A tailored PCa gene panel allowed us to stratify metastatic castration-resistant prostate cancer (mCRPC) patients with clinical outcomes. In addition, our findings suggest that targeted CTC transcriptome profiling may be predictive of therapy response.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling of Circulating Tumor Cells to Predict Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer

Groen

Kloots

Englert

et al. 2023

IJMS

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“…FOXA1 is a crucial transcription factor functionally involved in the initiation and development of many types of cancers, including PCa. To our knowledge, previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes; comprehensive analysis of its regulatory ceRNA network of lncRNAs, however, has not been attempted ( 35 ). Accordingly, in this research, we devoted to establishing a FOXA1-related ceRNA triple network in PCa, as well as associating it with prognosis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer

Yang

Chen²,

Quan³

et al. 2023

Front. Oncol.

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BackgroundProstate cancer (PCa) is the second most common cause of cancer-related deaths in American men. Even though increasing evidence has disclosed the competitive endogenous RNA (ceRNA) regulatory networks among cancers, the complexity and behavior characteristics of the ceRNA network in PCa remain unclear. Our study aimed to investigate the forkhead box A1 (FOXA1)-related ceRNA regulatory network and ascertain potential prognostic markers associated with PCa.MethodsRNA sequence profiles downloaded from The Cancer Genome Atlas (TCGA) were analyzed to recognize differentially expressed genes (DEGs) derived from tumor and non-tumor adjacent samples as well as FOXA1low and FOXA1high tumor samples. The enrichment analysis was conducted for the dysregulated mRNAs. The network for the differentially expressed long non-coding RNA (lncRNA)-associated ceRNAs was then established. Survival analysis and univariate Cox regression analysis were executed to determine independent prognostic RNAs associated with PCa. The correlation between DUSP2 and immune cell infiltration level was analyzed. Tissue and blood samples were collected to verify our network. Molecular experiments were performed to explore whether DUSP2 is involved in the development of PCa.ResultsA ceRNA network related to FOXA1 was constructed and comprised 18 lncRNAs, 5 miRNAs, and 44 mRNAs. The MAGI2-AS3~has-mir-106a/has-mir-204~DUSP2 ceRNA regulatory network relevant to the prognosis of PCa was obtained by analysis. We markedly distinguished the MAGI2-AS3/DUSP2 axis in the ceRNA. It will most likely become a clinical prognostic model and impact the changes in the tumor immune microenvironment of PCa. The abnormal MAGI2-AS3 expression level from the patients’ blood manifested that it would be a novel potential diagnostic biomarker for PCa. Moreover, down-expressed DUSP2 suppressed the proliferation and migration of PCa cells.ConclusionsOur findings provide pivotal clues to understanding the role of the FOXA1-concerned ceRNA network in PCa. Simultaneously, this MAGI2-AS3/DUSP2 axis might be a new significant prognostic factor associated with the diagnosis and prognosis of PCa.

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“…Here comes the technology of organ-on-a-chip. To address critical biomedical issues, such technology, developed from in vitro cell growth to circumvent in vivo system restrictions, seems to be the most relevant alternative that can reproduce particular organ biological functions [ 49 , 50 ].…”

Section: Organs-on-chips: the State-of-the-art Technologymentioning

confidence: 99%

Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation

et al. 2022

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Over the decades, conventional in vitro culture systems and animal models have been used to study physiology, nutrient or drug metabolisms including mechanical and physiopathological aspects. However, there is an urgent need for Integrated Testing Strategies (ITS) and more sophisticated platforms and devices to approach the real complexity of human physiology and provide reliable extrapolations for clinical investigations and personalized medicine. Organ-on-a-chip (OOC), also known as a microphysiological system, is a state-of-the-art microfluidic cell culture technology that sums up cells or tissue-to-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology, and it has been developed to fill the gap between in vitro experimental models and human pathophysiology. The wide range of OOC platforms involves the miniaturization of cell culture systems and enables a variety of novel experimental techniques. These range from modeling the independent effects of biophysical forces on cells to screening novel drugs in multi-organ microphysiological systems, all within microscale devices. As in living biosystems, the development of vascular structure is the salient feature common to almost all organ-on-a-chip platforms. Herein, we provide a snapshot of this fast-evolving sophisticated technology. We will review cutting-edge developments and advances in the OOC realm, discussing current applications in the biomedical field with a detailed description of how this technology has enabled the reconstruction of complex multi-scale and multifunctional matrices and platforms (at the cellular and tissular levels) leading to an acute understanding of the physiopathological features of human ailments and infections in vitro.

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Transcriptional network involving ERG and AR orchestrates Distal-less homeobox-1 mediated prostate cancer progression

Cited by 28 publications

References 80 publications

Transcriptome Profiling of Circulating Tumor Cells to Predict Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer

Transcriptome Profiling of Circulating Tumor Cells to Predict Clinical Outcomes in Metastatic Castration-Resistant Prostate Cancer

Comprehensive analysis of the FOXA1-related ceRNA network and identification of the MAGI2-AS3/DUSP2 axis as a prognostic biomarker in prostate cancer

Organs-on-Chips Platforms Are Everywhere: A Zoom on Biomedical Investigation

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