ELF4 is a target of miR-124 and promotes neuroblastoma proliferation and undifferentiated state
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ABSTRACT:
PROVIDER: PRJNA517477 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8496530.fastq.gz | Fastqsanger.gz | |||
| SRR8496531.fastq.gz | Fastqsanger.gz | |||
| SRR8496532.fastq.gz | Fastqsanger.gz | |||
| SRR8496533.fastq.gz | Fastqsanger.gz | |||
| SRR8496534.fastq.gz | Fastqsanger.gz |
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Project description:We performed RNA-seq to identify the transcriptional targets of ELF4 in BE-(2)-C neuroblastoma cells.
2019-10-01 | GSE125772 | GEO
Project description:13-Cis-retinoic acid (RA) is typically used in postremission maintenance therapy in patients with neuroblastoma. However, side effects and recurrence are often observed. We investigated the use of miRNAs as a strategy to replace RA as promoters of differentiation. miR-124 was identified as the top candidate in a functional screen. Genomic target analysis indicated that repression of a network of transcription factors (TF) could be mediating most of miR-124's effect in driving differentiation. To advance miR-124 mimic use in therapy and better define its mechanism of action, a high-throughput siRNA morphologic screen focusing on its TF targets was conducted and ELF4 was identified as a leading candidate for miR-124 repression. By altering its expression levels, we showed that ELF4 maintains neuroblastoma in an undifferentiated state and promotes proliferation. Moreover, ELF4 transgenic expression was able to counteract the neurogenic effect of miR-124 in neuroblastoma cells. With RNA sequencing, we established the main role of ELF4 to be regulation of cell-cycle progression, specifically through the DREAM complex. Interestingly, several cell-cycle genes activated by ELF4 are repressed by miR-124, suggesting that they might form a TF-miRNA regulatory loop. Finally, we showed that high ELF4 expression is often observed in neuroblastomas and is associated with poor survival. IMPLICATIONS: miR-124 induces neuroblastoma differentiation partially through the downregulation of TF ELF4, which drives neuroblastoma proliferation and its undifferentiated phenotype.
| S-EPMC6942226 | biostudies-literature
Project description:To elucidate how ELF4 confers anti-growth activity, gene expression profiles were compared between wildtype- and mutant-expressing T3M-1 Cl-10 cells with the use of DNA microarrays. T3M-1 Cl-10 cells were infected with a mock retrovirus or virus generated from pMXS-ires-EGFP expressing ELF4 or ELF4(L211M), and EGFP?positive fractions were purified with a cell sorter. Thus gene expression profiling of purely mock/ELF4/ELF4(L211M)-expressing cells was performed with SurePrint G3 Human Gene Expression 8×60K v2 Microarray.
2013-12-04 | E-GEOD-52855 | biostudies-arrayexpress
Project description:Transcription factors that regulate quiescence, proliferation, and homing of lymphocytes are critical for effective immune system function. In the present study, we demonstrated that the transcription factor ELF4 directly activates the tumor suppressor KLF4 downstream of T cell receptor (TCR) signaling to induce cell cycle arrest in naïve CD8+ T cells. Elf4- and Klf4-deficient mice accumulated CD8+CD44hi T cells during steady-state conditions and generated more memory T cells after immunization. The homeostatic expansion of CD8+CD44hi T cells in Elf4-null mice resulted in a redistribution of cells to non-lymphoid tissue due to reduced expression of the transcription factor KLF2, and the surface proteins CCR7 and CD62L. This work describes the combinatorial role of lymphocyte-intrinsic factors in the control of T cell homeostasis, activation and homing.
2009-03-24 | GSE15324 | GEO
Project description:ELF4 (also known as MEF) is a member of the ETS family of transcriptional factors. While an oncogenic role has been demonstrated for ELF4 mainly in hematopoietic malignancies, its definitive function in human carcinogenesis is not clear yet. Here we demonstrate that a wide array of human tumors carry somatic, loss-of-function mutations in ELF4 for its transcriptional activity, and restoring its function exerts anti-proliferative effects. To further explore the tumor suppressive function of ELF4, its binding sites were searched among the human genome with the use of chromatin immunoprecipitation coupled with sequencing (ChIP-seq). Examination of binding site for FLAG-immunoprecipitated mock, ELF4 (WT) and ELF4 (L211M) with each input sample as a control.
2016-03-01 | E-GEOD-53357 | biostudies-arrayexpress
Project description:To study how miR-124 and VAMP3 may regulate human neuroblastoma, thee human neuroblastoma cell line SK-N-SH were transiently transfected to overexpress miR-124 or VAMP3, and total RNA was isolated 48 hours after transfection and subject to RNA-seq.
2023-10-23 | GSE240277 | GEO
Project description:ELF4 (also known as MEF) is a member of the ETS family of transcriptional factors. While an oncogenic role has been demonstrated for ELF4 mainly in hematopoietic malignancies, its definitive function in human carcinogenesis is not clear yet. Here we demonstrate that a wide array of human tumors carry somatic, loss-of-function mutations in ELF4 for its transcriptional activity, and restoring its function exerts anti-proliferative effects. To further explore the tumor suppressive function of ELF4, its binding sites were searched among the human genome with the use of chromatin immunoprecipitation coupled with sequencing (ChIP-seq).
2016-03-01 | GSE53357 | GEO
Project description:High-risk 11q deleted neuroblastomas (NBs) typically display an undifferentiated/poorly differentiated morphology. NB is thought to develop from Schwann cell precursors (SCPs) and un-differentiated neural crest derived cells (NCC). It is therefore vital to understand the mechanisms involved in the block of differentiation. We showed that an important and novel role for oncogenic ALK-ERK1/2-SP1 signaling may be the maintenance of an undifferentiated state of transformed NC-derived progenitors that is achieved by repression of DLG2, a tumor suppressor in NB. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors (SCP) become chromaffin cells of the adrenal gland. The importance of SP1 and DLG2 in this process is highlighted by our findings that restoring DLG2 expression spontaneously drives NB differentiation. Further, genetic analysis of high-risk 11q deletion NB patient identified genetic lesions in the DLG2 gene, Our data also suggest that further exploration of other ‘bridge genes’ may help to better understand the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to NB.
2020-11-25 | PXD017946 | Pride
Project description:To elucidate how ELF4 confers anti-growth activity, gene expression profiles were compared between wildtype- and mutant-expressing T3M-1 Cl-10 cells with the use of DNA microarrays.
2013-12-04 | GSE52855 | GEO
Project description:Transcription factors specialized to limit the destructive potential of inflammatory immune cells remain ill-defined. We discovered loss-of-function variants in the X-linked ETS transcription factor gene ELF4 in multiple unrelated male patients with early-onset mucosal autoinflammation and inflammatory bowel disease (IBD) characteristics including fevers and ulcers that responded to IL-1, TNF, or IL-12p40 blockade. Using cells from patients and two newly generated mouse models, we uncovered hyperinflammatory responses of ELF4-mutant macrophages to a range of innate stimuli. Mechanistically, Elf4 in macrophages both sustained expression of anti-inflammatory genes such as Il1rn and limited upregulation of inflammation amplifiers, including S100A8, Lcn2, Trem1, and neutrophil chemoattractants. Indeed, therapeutic Trem1 blockade reversed inflammation and intestine pathology in Elf4-mutant mice challenged with lipopolysaccharide in vivo. Thus, the ELF4 transcription factor restrains inflammation and protects against mucosal disease, a discovery with broad translational relevance for human inflammatory diseases such as IBD.
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