LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA902381 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22314942.fastq.gz | Fastqsanger.gz | |||
| SRR22314943.fastq.gz | Fastqsanger.gz | |||
| SRR22314944.fastq.gz | Fastqsanger.gz | |||
| SRR22314945.fastq.gz | Fastqsanger.gz | |||
| SRR22314946.fastq.gz | Fastqsanger.gz |
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Project description:Resistance to endocrine therapy represents a major threat to patients with estrogen receptor α positive (ERα+) breast cancer. The development of resistance is mainly through activating E2F signaling. However, the mechanisms that govern E2F1 activity in these resistant cells remain poorly understood. Here, we identify Actin Gamma 1 Pseudogene 25 (AGPG) as a lncRNA whose expression is driven by epigenomic activation of enhancer in endocrine resistant breast cancer cells. High expression of AGPG is associated with poor survival of ERα+ breast cancer, especially in patients receiving endocrine therapy. Stable knockdown and overexpression of AGPG demonstrate that AGPG promotes endocrine resistance, cell cycle progression, cell proliferation in vitro and in vivo. AGPG functions by direct binding purine rich element binding protein α (PURα), a transcription factor repressing E2F1 signaling and sensitized ERα+ breast cancer cells to endocrine therapy. Via binding to the region responsible for PURα/E2F1 interaction in PURα protein, AGPG releases E2F1 from PURα, leading to activation of E2F1 signaling in ERα+ breast cancer cells. Clinically, E2F1 target genes are strongly correlated with AGPG and PURα expression. Thus, our study reveals AGPG as a promising biomarker and potential therapeutic target in breast cancer.
2023-07-12 | GSE218130 | GEO
Project description:Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Most lncRNA have been proven to have biological and clinical significance in acute myeloid leukemia (AML), but further studies remain to be needed. In this study, we investigated lncRNA NR-104098 in AML and its specific mechanism. The microarray analysis was performed on NB4 cells. Based on the related analysis results, we identified that lncRNA NR-104098 is a suppressor gene that is significantly upregulated in AML cells. lncRNA NR-104098 could inhibit proliferation and induce differentiation in AML cells in vitro, and also play main role in the mouse xenografts. Mechanically, it was confirmed that lncRNA NR-104098 may effectively inhibit EZH2 transcription by directly binding E2F1 and recruiting E2F1 to EZH2 promoter. In addition, ATPR can significantly increase the expression of lncRNA NR-104098, whereas knocking down NR104098 can inhibit the inhibitory effect of ATPR on the proliferation and induction differentiation of AML cells. Taken together, these results lead to a deeper insight into the mechanism of ATPR induces AML differentiation and inhibits proliferation by inhibiting EZH2 on transcriptional level.
2020-02-20 | GSE145168 | GEO
Project description:*** This submission includes RNA data, with DNA files available under a different accession number*** Purpose: Endocrine therapy resistance remains the greatest challenge for treating hormone receptor positive breast cancer patients. We aim to identify molecular mechanisms underlying endocrine therapy resistance through in-depth genomic analysis of patient samples. Experimental Design: We collected tumors from 35 estrogen receptor positive breast cancer patients receiving endocrine therapy, of which 3 patients had intrinsic resistance and 19 patients developed acquired resistance. For each patient, multiple tumor specimens were collected during the course of treatment. We performed DNA whole exome sequencing and RNA sequencing on all tumor samples. DNA mutations, copy number alterations and RNA gene expression data were analyzed through supervised analyses comparing paired sensitive and resistant tumor samples to identify molecular features related to endocrine therapy resistance. Results: We identified mutations enriched in resistant tumors including ESR1 and GATA3. ESR1 D538G variant confers endocrine therapy resistance while E380Q variant confers hypersensitivity. We demonstrate that resistant tumors had distinct gene expression profiles and elevated signaling pathways including ER, HER2, GATA3, AKT, RAS and p63 signaling. Integrated analysis for individual patient highlighted the heterogeneity of endocrine therapy resistance mechanisms. Conclusions: Our results suggest that mechanisms underlying endocrine therapy resistance are highly heterogeneous with diverse changes in genomic and transcriptomic levels.
2022-09-01 | E-MTAB-9917 | biostudies-arrayexpress
Project description:E2F transcription factors are known regulators of the cell cycle, proliferation, apoptosis and differentiation. We reveal an essential role for E2F1 in liver through the regulation of glycolysis and lipogenesis. E2F1 deficiency leads to a decreased in glycolysis and de novo synthesis of fatty acids in hepatocytes. ChIP-Seq was performed to determine direct tagets of E2F1 in hepatocytes. We highlight that E2F1 directly binds the promoters of genes implicated in metabolic process and notably key lipogenic genes to control these pathways.
2015-12-01 | GSE74006 | GEO
Project description:lncRNA expression profiles and lncRNA NR-104098 inhibits AML proliferation and induces differentiation through repressing EZH2 transcription by interacting with E2F1
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Project description:Effect of FOXO knockdown on E2F1-mediated transcription
2012-07-06 | GSE39136 | GEO
Project description:Purpose: dose response analysis of E2F1 target genes expression in flow-sorted fractions with increasing amounts of fluorescently labled E2F1 Methods:U2OS pTRIPZ-YFP-ER-E2F1 cells were grown in full serum-containing growth medium and treated with 500 ng/ml doxycycline for 48 hours followed by addition of 90 nM OHT for an additional 20 hours. Cells from different YFP fractions were sorted by flow cytometry. mRNA profiles were generated by deep sequencing using Illumina HiSeq 4000. Results: different target genes have different E2F1 activation thresholds. Numerous proliferation-related target genes are induced already by the lowest E2F1-levels. Intermediate E2F1 levels induce cdk inhibitors, which might be responsible for cell cycle arrest. Finally, although some apoptotic E2F1 targets are induced already by low E2F1 levels, many key apoptotic genes require higher E2F1 levels for induction. Conclusions: induction of different cell fates by increasing E2F1 levels might pertain to differential affinities of the targets.
2017-08-22 | GSE93365 | GEO
Project description:Identification of E2F1-regulated genes that modulate the transition from quiescence into DNA synthesis, or have roles in apoptosis, signal transduction, membrane biology, and transcription repression. Keywords: other
2003-07-16 | GSE498 | GEO
Project description:Effect of FOXO knockdown on E2F1-mediated transcription U2OS cells stably expressing ER-E2F1 were infected with two different lentiviruses both targeting FOXO1 and FOXO3 or control virus encoding scrambled sequence. Twenty four hours post infection medium was replaced to serum-free DMEM for 24 hours. Then medium was replaced to serum-free DMEM with or without 20 nM 4-hydroxy tamoxifen for 6 hours.
2012-07-05 | E-GEOD-39136 | biostudies-arrayexpress
Project description:E2F1 induces hundreds of protein-coding genes influencing diverse signaling pathways but much less is known about its non-coding RNA targets. For identifying E2F1-dependent oncogenic long non-coding RNAs (lncRNAs), we carried out genome-wide transcriptome analysis and discovered an lncRNA, EMSLR, which is induced both in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). EMSLR depletion blocks the cells in G1 phase and inhibits the clonogenic ability indicating that it is essential for the tumor-related phenotypes. We discovered that EMSLR represses the promoter activity of another lncRNA, LncPRESS1, which is located 6.9 kb upstream of EMSLR and they display an inverse expression pattern in lung cancer cell lines. Depletion of C-MYC results in downregulation of EMSLR and simultaneous upregulation of EMSLR target LncPRESS1, exemplifying how C-MYC and E2F1 signal transduction pathways control the network of lncRNA genes to modulate cell proliferation and differentiation.
| S-EPMC8847401 | biostudies-literature