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SETD7 functions as a transcription repressor in prostate cancer via methylating FOXA1 [RNA-seq]

ABSTRACT: To determine the transcriptional impact of SETD7,MLL1 silencing in CRPC cells, we performed an RNA-seq analysis in those 22Rv1 stable cell lines (under hormone-depleted conditions)

ORGANISM(S): Homo sapiens

PROVIDER: GSE218093 | GEO | 2023/08/23

REPOSITORIES: GEO

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SETD7 functions as a transcription repressor in prostate cancer via methylating FOXA1 [ChIP-seq]

Project description:We recently reported that in prostate cancer LSD1 can demethylate the lysine 270 of FOXA1 to stabilize FOXA1 chromatin binding and thus can enhance the activities of AR and other transcription factors that require FOXA1 as a pioneer factor. However, the methyltransferase that can methylate FOXA1 and negatively regulate the LSD1-FOXA1 oncogenic axis remains unknown. SETD7 is initially identified as a transcriptional activator through methylating histone 3 lysine 4 but can also function as a methyltransferase on other non-histone substrates. However, its function in PCa remains poorly understood. In this study, we found that SETD7 confers tumor suppressor activity in PCa cells and that loss of SETD7 expression is significantly associated with PCa progression and tumor aggressiveness. Mechanistically, we found that SETD7 primarily acts as a transcriptional repressor in CRPC cells by functioning as a methyltransferase of FOXA1-K270 to disrupt FOXA1-mediated transcription. Overall, our study provides novel mechanistic insights into the tumor-suppressive and transcriptional repression activities of SETD7 in mediating PCa progression and therapy resistance.

2023-08-23 | GSE218092 | GEO

SETD7 functions as a transcription repressor in prostate cancer via methylating FOXA1

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-23 | GSE218094 | GEO

Essential Roles of SETD7 as Transcriptional Activator and Co-regulator of H3K36me in Cardiac Lineage Commitment

Project description:Coordinated epigenome alteration is fundamental for cardiac development. However, the precise mechanisms by which epigenetic modifying enzymes regulate cardiac development are still unclear. Here we identify SET domain containing protein 7 (SETD7) as a key regulator of cardiac differentiation. ChIP-seq reveals that SETD7 has distinct groups of target genes and regulates its stage-specific expression during cardiomyocyte differentiation, which is crucial for lineage commitment. We find SETD7 associates with stage-specific co-factors, such as SWI/SNF chromatin remodeling factors during mesodermal formation and transcription factor NKX2-5 in cardiac progenitor differentiation. Cross-analysis of epigenetic modifications shows that SETD7 recognizes and binds with active histone marker H3K36 methylation on gene-body region of its target genes. We further demonstrate SETD7 is required for functional properties of terminally differentiated cardiomyocytes. Together, our results suggest unidentified roles of SETD7 in cardiac lineage commitment and provide new insights into the crosstalk between epigenetic dynamics and epigenetic modifying enzymes.

2018-04-17 | GSE107785 | GEO

SETD7 promotes lateral plate mesoderm formation by modulating the Wnt/b-catenin signaling pathway

Project description:Investigating the role of SETD7 during human hematopoietic development

2023-09-11 | GSE228287 | GEO

Effects of OCT1 knockdown in castration-resistant prostate cancer cells

Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Although initially hormone-deprovation therapy is effective to inhibit cancer progression, most of cancers relapse as castration-resistant prostate cancer (CRPC). Therefore, we examined the effect of AR interacting partner OCT1 in CRPC cells. In order to investigate the OCT1 function in CRPC cells, we performed gene expression in AR-positive CRPC cell line, 22Rv1, after siOCT1 treatment. We also treated cells with vehicle or dihydrotestosterone (DHT) to analyzed the effects of OCT1 on AR function.

2019-03-01 | GSE123517 | GEO

Effects of OCT4/NRF1 knockdown in castration-resistant prostate cancer cells

Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Although initially hormone-deprovation therapy is effective to inhibit cancer progression, most of cancers relapse as castration-resistant prostate cancer (CRPC). In this study, we examined the effect of OCT4 or NRF1 knockdown in CRPC cells. In order to investigate the OCT4 and NRF1 function in CRPC cells, we performed gene expression in AR-positive CRPC cell line, 22Rv1, AR-negative CRPC cell lines, PC3-CR (Cabazitaxel resistant), DU145, and DU145-CR, after siOCT4 (10 nM) or siNRF1 (10 nM) treatment. We also treated cells with vehicle, ribavirin (riba), or dihydrotestosterone (DHT) to analyzed the effects of thiese drug treatments.

2021-05-01 | GSE146656 | GEO

RNA sequencing in 22RV1 cells stably expressing shLuc, shIMPA1, shIMPDH2

Project description:We investigated gene expession profiles of IMPA1 knockdown and IMPDH2 knockdown in CRPC 22RV1 cells by using RNA-seq

2024-08-15 | GSE270564 | GEO

Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer II

Project description:Prostate-specific membrane antigen (PSMA) has emerged as an important therapeutic target in metastatic castration-resistant prostate cancer (CRPC). However, not all patients respond to PSMA-targeted therapy, in part due to heterogeneity of tumor expression of the target PSMA. Furthermore, loss of PSMA expression develops in up to 15-20% of patients with CRPC, and the underlying mechanisms remain poorly defined. In this study, we developed an orthotopic xenograft model of CRPC using 22Rv1 cell line, we observed lower PSMA expression in liver lesions versus other sites of metastatic disease, suggesting a potential role of the microenvironment in modulating PSMA expression. To facilitate investigation of PSMA-suppression, we cultured and immortalized a liver metastasis of 22Rv1 metastatic xenograft model in vitro as a new cell line (22Rv1-LMD) which remained AR-positive and PSMA-negative.

2023-01-30 | GSE211450 | GEO

Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I

2023-01-30 | GSE211448 | GEO

Spermidine synthase regulates extracellular vesicle secretion in castration resistant prostate cancer.

Project description:Extracellular vesciles (EVs) have an important role in the tumor progression. However, the precise regulatrory mechanisms of EV secretion has not been clarified yet. We performed quantitive high-throughput screening to eluciade the key miRNAs for EV biogenesis in castration resistant prostate cancer (CRPC) using 22RV1 cells, and miR-1908 was selected as the miRNA regulating EV biogenesis in CRPC. To identify the genes that could be targeted by miR-1908, we performed mRNA micorarray analysis in 22RV1 after transfected of miR-1908 mimic or control miRNA.

2020-06-21 | GSE143350 | GEO

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