This SuperSeries is composed of the SubSeries listed below.
Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation.
Specimen part, Treatment
View SamplesTumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment. Tumor microenvironment coevolves with and simultaneously sustains cancer progression. Reactive fibroblasts found in prostate cancer (PCa), known as cancer associated fibroblasts (CAF), have been indeed shown to fuel tumor development and metastasis by mutually interacting with PCa cells. Little is known about the molecular mechanisms that lead to activation of CAFs from tissue-resident fibroblasts, circulating marrow-derived fibroblast progenitors or mesenchymal stem cells. Through integrated gene and microRNA expression profiling, here we showed that transcriptome of CAFs isolated from prostate tumors strictly resembles that of normal fibroblasts stimulated in vitro with interleukin-6 (IL6), thus confirming the capability of the cytokine to promote acquisition of an activated and cancer-promoting phenotype, and, for the first time, proving that IL6 is able per se to induce all the complex transcriptional changes characteristic of patient-derived CAFs. Comparison with publicly available datasets, however, suggested that prostate CAFs may be alternatively characterized by IL6 and TGF-related signatures, indicating that either signal, depending on the context, tumor stage and etiology, may concur to fibroblast activation. Our analyses also highlighted pathways relevant for induction of reactive stroma, including genes the role of which in fibroblast activation is still to be explored. In addition, we revealed a role for muscle-specific miR-133b as a soluble factor secreted by activated fibroblasts to support paracrine activation of non-activated fibroblasts or promote tumor progression. Overall, in this study we provided insights on the molecular mechanisms driving fibroblast activation in prostate cancer, thus contributing to identify novel hits for the development of therapeutic strategies targeting the crucial interplay between tumor cells and their microenvironment.
Integrated gene and miRNA expression analysis of prostate cancer associated fibroblasts supports a prominent role for interleukin-6 in fibroblast activation.
Specimen part, Treatment
View SamplesWe aimed at analyzing the transcriptome changes associated with SPOP mutation in DU145 cells
SPOP Deregulation Improves the Radiation Response of Prostate Cancer Models by Impairing DNA Damage Repair.
Cell line
View SamplesThe study was aimed at identifying genes directly or indirectly regulated by miR-205 in the prostate. To this purpose, DU145 prostate cancer cells, which express miR-205 at very low levels, were transfected with miR-205 synthetic precursor and consequent alterations of gene expression analyzed using a microarray approach.
miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with the deletion of a portion of the Alu element from MIR205HG transcript
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Cell line
View SamplesWe aimed at analyzing the transcriptome changes associated with MIR205HG knock-down in RWPE-1 cells
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
No sample metadata fields
View SamplesPluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. Overall design: RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.
Zfp281 Coordinates Opposing Functions of Tet1 and Tet2 in Pluripotent States.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer.
Cell line
View SamplesContext: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive- aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions:GCcytokine/chemokinemRNAswere identified and analyzed by gene-chip microarrays/ qPCR before and after culture withhumanchorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.
Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome.
Specimen part
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