<i><scp>EWSR</scp>1/<scp>ELF</scp>5</i> induces acute myeloid leukemia by inhibiting p53/p21 pathway

Endo, Akifumi; Tomizawa, Daisuke; Aoki, Yuki; Morio, Tomohiro; Mizutani, Shuki; Takagi, Motoki

doi:10.1111/cas.13080

Cited by 16 publications

(6 citation statements)

References 46 publications

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“… 32 , 33 , 34 , 35 The other two proteins, paraspeckle component 1 (PSPC1) and EWS RNA binding protein 1 (EWSR1), were closely related with cancers. 36 , 37 , 38 In the KH-containing PRRBC family, we only predicted KH RNA binding domain containing signal transduction-associated 1 (KHDRBS1) ( Figure 5 J). Of note, EWSR1 was a member of both RRM- and ZnF_RBZ-containing PRRBC families ( Figure 5 J).…”

Section: Resultsmentioning

confidence: 99%

A positive feedback circuit between RN7SK snRNA and m6A readers is essential for tumorigenesis

Xu¹,

Ma²,

Zhang³

et al. 2023

Molecular Therapy

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Section: Resultsmentioning

confidence: 99%

A positive feedback circuit between RN7SK snRNA and m6A readers is essential for tumorigenesis

Xu¹,

Ma²,

Zhang³

et al. 2023

Molecular Therapy

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“…Several DE isoforms identified in SF mutated patients correspond to cancer-related genes, many of which have a known role in AML. Specifically, genes with DE isoforms included, but were not limited to BRD4 [34], EWSR1 [35] and YBX1 [36] in SRSF2 (P95H) mutated samples, CUX1 [37], DEK [15,38] and EZH1 [39] in U2AF1 (S34F) mutated samples, as well as PTK2 [40] in SF3B1 (K700E) mutated patients (Tables S7.1-S7.2).…”

Section: Resultsmentioning

confidence: 99%

Clinical presentation and differential splicing ofSRSF2, U2AF1andSF3B1mutations in patients with Acute Myeloid Leukaemia

Bamopoulos

Batcha²,

Jurinović

et al. 2020

Preprint

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Previous studies have demonstrated that splicing factor mutations are recurrent events in hematopoietic malignancies. Their clinical characteristics and aberrant splicing patterns have been explored in myelodysplasia, however, their functional consequences in acute myeloid leukaemia are largely unknown. The aim of this study was the comprehensive clinical and functional analysis of mutations in the three most commonly afflicted splicing factor genes: SRSF2, U2AF1 and SF3B1. To this end, we examined the prognostic role of splicing factor mutations in two large independent cohorts, encompassing a total of 2678 acute myeloid leukaemia patients treated with intensive chemotherapy. The clinical analysis was complemented by RNA-sequencing of 246 patients to identify targets of splicing dysregulation. Results were validated in an additional RNA-sequencing dataset of 177 patients. Patients with splicing factor mutations show inferior relapse-free and overall survival, however, these mutations do not represent independent prognostic markers. Differential isoform expression analysis revealed a characteristic expression profile for each splicing factor mutation with a strong dysregulation of several isoforms. Furthermore, by establishing a custom differential splice junction usage pipeline we accurately detected aberrant splicing in splicing factor mutated samples. Mutated samples were characterized by predominantly decreased splice junction utilization of a large number of genes. A large proportion of differentially used spliced junctions were novel. Targets of splicing dysregulation included several genes with a known role in acute myeloid leukaemia. In SRSF2(P95H) mutants we further explored the possibility of a cascading effect through the dysregulation of the splicing pathway. Taken together, our findings suggest that splicing factor mutations does not represent independent prognostic markers. However, they do have genome-wide consequences on gene splicing leading to dysregulated isoform expression of several genes.

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“…ELF3-5, as members of a transcription factor family, have been implicated in regulating tumor progression through various signaling pathways. ELF3 can promote resistance in gallbladder cancer cells via the PKMYT1/CDK1 signaling pathway ( 37 ), whereas ELF5 can inhibit the p53/p21 pathway, leading to the induction of acute myeloid leukemia ( 38 ). In glioblastoma, ELF4 controls genes associated with receptor tyrosine kinase and receptor tyrosine kinase pathways ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of E47‑like factors and verification of ELF4 in clear cell renal cell carcinoma

Lü

Zhang

et al. 2023

Oncol Lett

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Clear cell renal cell carcinoma (ccRCC) is the most prominent subtype of renal cancer and E47-like factors (ELFs) are important in tumorigenesis; however, the specific role of key ELFs in ccRCC remains unclear. The present study comprehensively analyzed RNA sequencing and clinical data from multiple databases, and identified differentially expressed ELFs (ELF3-5) in ccRCC. The DNA promoter methylation, genetic variation and clinical significance of ELF3-5 in ccRCC were analyzed using the cBioPortal and UALCAN databases. The association between ELF3-5 and multiple immune cell infiltration was analyzed using Tumor Immune Estimation Resource. Subsequently, ELF4 was selected and its association with biological functions was assessed. Cell counting kit-8 (CCK-8), colony formation, Transwell, macrophage chemotaxis and polarization assays were conducted to validate the functions of ELF4. Notably, the mRNA expression levels of ELF4 were significantly upregulated in ccRCC, whereas ELF3 and ELF5 mRNA expression levels were significantly downregulated. Clinical significance analysis revealed that ELF4 showed a high clinical significance with tumor grade, clear cell type A and B subtypes, and incidence rates of amplification in genetic variation. Further analyses indicated that ELF4 may be involved in multiple immune cell differentiation. Additionally, cell experiments revealed that ELF4 inhibition downregulated 769-P and 786-O proliferation, migration and invasion. Knockdown of ELF4 in cancer cells also inhibited M2 macrophage polarization and chemotaxis towards 769-P and 786-O cells. Conclusively, the present findings indicated the clinical significance of ELF4 in ccRCC, and verified its key role in driving cell proliferation, migration and invasion, and promoting M2 macrophage polarization and chemotaxis in ccRCC.

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EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway

Cited by 16 publications

References 46 publications

A positive feedback circuit between RN7SK snRNA and m6A readers is essential for tumorigenesis

A positive feedback circuit between RN7SK snRNA and m6A readers is essential for tumorigenesis

Clinical presentation and differential splicing ofSRSF2, U2AF1andSF3B1mutations in patients with Acute Myeloid Leukaemia

Comprehensive analysis of E47‑like factors and verification of ELF4 in clear cell renal cell carcinoma

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