Similar Datasets
Project description:Identification of novel transcription factors that regulate prostate cancer cell metabolism
| PRJNA635396 | ENA
Project description:To identify which genes are regulated by KLF5 and its acetylation, we performed RNA-Seq and bioinformatics analyses in KLF5-null prostate cancer cells expressing KLF5, KLF5KR, and KLF5KQ.
2020-12-19 | GSE161950 | GEO
Project description:To identify which genes are directly regulated by KLF5 and its acetylation, we performed ChIP-Seq and bioinformatics analyses in KLF5-null prostate cancer cells expressing KLF5, KLF5KR, and KLF5KQ.
2020-12-19 | GSE161949 | GEO
Project description:Advanced prostate cancer (PC) can be treated with endocrine therapies that inhibit transcriptional activity of the androgen receptor (AR). However, PC will ultimately evolve under the selection pressure of these therapies and progress to a lethal phenotype termed castration-resistant PC (CRPC). Recent studies suggest that de-differentiation away from an AR-driven luminal cell identity may be a key, early step. However, early therapy-induced mechanisms of prostate cancer cell de-differentiation are poorly understood. Here we show that the stem cell transcription factor Kruppel-like factor 5 (KLF5) is transcriptionally repressed by AR, and de-repressed by enzalutamide. KLF5 expression is high in a subset of CRPC tissues, but low in primary adenocarcinoma. KLF5 functioned as oncogene in CPRC cells, promoting cellular migration, anchorage-independent growth, expression of basal cell markers, and transcriptional signatures of CRPC lineage plasticity, but had modest effects on cell proliferation. Chromatin immuno-precipitation (ChIP)-sequencing, RNA-sequencing, and co-immunoprecipitation experiments established a physical interaction between KLF5 and AR, and integrative analysis revealed that KLF5 and AR drive opposing transcriptional programs. We identified ERBB2 as a point of transcriptional convergence that was activated by KLF5 and repressed by AR. Accordingly, KLF5 expression levels in CRPC tissues correlated with predicted sensitivity to the dual EGFR inhibitor lapatanib, and the ERBB2-specific inhibitor mubritinib blocked KLF5-driven cell migration. Collectively, these findings implicate KLF5 as an AR-suppressed oncogene that drives early steps in CRPC de-differentiation and disease progression.
2021-09-21 | GSE148807 | GEO
Project description:Advanced prostate cancer (PC) can be treated with endocrine therapies that inhibit transcriptional activity of the androgen receptor (AR). However, PC will ultimately evolve under the selection pressure of these therapies and progress to a lethal phenotype termed castration-resistant PC (CRPC). Recent studies suggest that de-differentiation away from an AR-driven luminal cell identity may be a key, early step. However, early therapy-induced mechanisms of prostate cancer cell de-differentiation are poorly understood. Here we show that the stem cell transcription factor Kruppel-like factor 5 (KLF5) is transcriptionally repressed by AR, and de-repressed by enzalutamide. KLF5 expression is high in a subset of CRPC tissues, but low in primary adenocarcinoma. KLF5 functioned as oncogene in CPRC cells, promoting cellular migration, anchorage-independent growth, expression of basal cell markers, and transcriptional signatures of CRPC lineage plasticity, but had modest effects on cell proliferation. Chromatin immuno-precipitation (ChIP)-sequencing, RNA-sequencing, and co-immunoprecipitation experiments established a physical interaction between KLF5 and AR, and integrative analysis revealed that KLF5 and AR drive opposing transcriptional programs. We identified ERBB2 as a point of transcriptional convergence that was activated by KLF5 and repressed by AR. Accordingly, KLF5 expression levels in CRPC tissues correlated with predicted sensitivity to the dual EGFR inhibitor lapatanib, and the ERBB2-specific inhibitor mubritinib blocked KLF5-driven cell migration. Collectively, these findings implicate KLF5 as an AR-suppressed oncogene that drives early steps in CRPC de-differentiation and disease progression.
2021-09-21 | GSE148806 | GEO
Project description:Cardiomyocytes are highly metabolic cells responsible for generating the contractile force that drives heart function. During fetal development and regeneration, these cells undergo active division but lose their proliferation activity in the adult heart. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the developmental functions of the transcription factor NFYa, which we previously identified from regenerating cardiomyocytes. We show that loss of NFYa profoundly alters cardiomyocyte composition, with a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as revealed by spatial and single-cell transcriptome analyses. NFYa-deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, contributing to the cardiac growth defect. NFYa acts as a transcriptional activator of mitochondrial metabolic genes as well as cell-cycle genes in cardiomyocytes through its interaction with the cofactor SP2, providing a direct link between metabolism and proliferation at the gene transcriptional level. Our study reveals a key role of NFYa in regulating cardiac growth before birth and a previously unrecognized transcriptional control mechanism of metabolic genes in the heart, and highlights the importance of mitochondrial metabolism during fetal heart development and regeneration.
2023-10-13 | GSE232962 | GEO
Project description:Cardiomyocytes are highly metabolic cells responsible for generating the contractile force that drives heart function. During fetal development and regeneration, these cells undergo active division but lose their proliferation activity in the adult heart. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the developmental functions of the transcription factor NFYa, which we previously identified from regenerating cardiomyocytes. We show that loss of NFYa profoundly alters cardiomyocyte composition, with a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as revealed by spatial and single-cell transcriptome analyses. NFYa-deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, contributing to the cardiac growth defect. NFYa acts as a transcriptional activator of mitochondrial metabolic genes as well as cell-cycle genes in cardiomyocytes through its interaction with the cofactor SP2, providing a direct link between metabolism and proliferation at the gene transcriptional level. Our study reveals a key role of NFYa in regulating cardiac growth before birth and a previously unrecognized transcriptional control mechanism of metabolic genes in the heart, and highlights the importance of mitochondrial metabolism during fetal heart development and regeneration.
2023-10-13 | GSE232961 | GEO
Project description:Cardiomyocytes are highly metabolic cells responsible for generating the contractile force that drives heart function. During fetal development and regeneration, these cells undergo active division but lose their proliferation activity in the adult heart. The mechanisms that coordinate their metabolism and proliferation are not fully understood. Here, we study the developmental functions of the transcription factor NFYa, which we previously identified from regenerating cardiomyocytes. We show that loss of NFYa profoundly alters cardiomyocyte composition, with a decrease in immature regenerative cells and an increase in trabecular and mature cardiomyocytes, as revealed by spatial and single-cell transcriptome analyses. NFYa-deleted cardiomyocytes exhibited reduced proliferation and impaired mitochondrial metabolism, contributing to the cardiac growth defect. NFYa acts as a transcriptional activator of mitochondrial metabolic genes as well as cell-cycle genes in cardiomyocytes through its interaction with the cofactor SP2, providing a direct link between metabolism and proliferation at the gene transcriptional level. Our study reveals a key role of NFYa in regulating cardiac growth before birth and a previously unrecognized transcriptional control mechanism of metabolic genes in the heart, and highlights the importance of mitochondrial metabolism during fetal heart development and regeneration.
2023-10-13 | GSE232960 | GEO
Project description:Long non-coding RNAs show highly tissue and disease specific expression profiles. We analyzed prostate cancer and normal adjacent prostate samples to identify cancer-specific transcripts and found 334 candidates, of which 15 were validated by RT-PCR. 8 Prostate cancer samples from radical prostatectomies, 12 samples from normal adjacent prostate, 12 samples from lymph node metastasis and 10 samples from transurethral resection of the prostrate were included in this study. These samples contained more than 70% cancer and less than 30% stromal tissue.
2015-03-02 | E-GEOD-59745 | biostudies-arrayexpress
Project description:Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR and forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify the nuclear factor I (NFI) family of transcription factors as novel FOXA1 binding proteins. All four family members (NFIA, NFIB, NFIC, and NFIX) can interact with FOXA1, and knockdown studies in androgen-dependent LNCaP cells determined that modulating expression of NFI family members results in changes in AR target gene expression. This effect is probably mediated by binding of NFI family members to AR target gene promoters, because chromatin immunoprecipitation (ChIP) studies found that NFIB bound to the prostate-specific antigen enhancer. Förster resonance energy transfer studies revealed that FOXA1 is capable of bringing AR and NFIX into proximity, indicating that FOXA1 facilitates the AR and NFI interaction by bridging the complex. To determine the extent to which NFI family members regulate AR/FOXA1 target genes, motif analysis of publicly available data for ChIP followed by sequencing was undertaken. This analysis revealed that 34.4% of peaks bound by AR and FOXA1 contain NFI binding sites. Validation of 8 of these peaks by ChIP revealed that NFI family members can bind 6 of these predicted genomic elements, and 4 of the 8 associated genes undergo gene expression changes as a result of individual NFI knockdown. These observations suggest that NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression.
| S-EPMC4042066 | biostudies-literature