TLE1 function and therapeutic potential in cancer

Yuan, Deshan; Yang, Xue; Yuan, Zhenpeng; Zhao, Yanqing; Guo, Junchao

doi:10.18632/oncotarget.13278

Cited by 22 publications

(19 citation statements)

References 51 publications

(57 reference statements)

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“…In cancer, its interaction with the Wnt-b-catenin pathway, where it competes with and displaces b-catenin, producing TLE1-T-cell factor-lymphoid enhancer factor complexes, is probably the most frequently described in the literature 35 ; however, it also interacts with other signalling pathways such as the Notch pathway and the phosphoinositide 3-kinase-Akt pathway in neoplastic processes and haematopoiesis, epithelial and neuronal differentiation. [36][37][38] The mechanism that results in TLE1 nuclear expression in DICER1-related tumours has not been described. We used immunohistochemistry to explore the possibility of Wnt pathway activation through b-catenin, and there was no nuclear translocation seen, although this result does not completely exclude Wnt pathway activation.…”

Section: Discussionmentioning

confidence: 99%

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin‐like enhancer 1 in primary intracranial sarcoma, DICER1‐mutant

Alexandrescu¹,

Meredith

Lidov³

et al. 2020

Histopathology

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Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant Aims: Primary intracranial sarcoma, DICER1-mutant is a recently described central nervous system tumour with specific genomic and DNA-methylation profiles. Although some of its histological features (focal spindle-cell morphology, intracytoplasmic eosinophilic granules, and focal heterologous differentiation) are common across most reported cases, the presence of significant histological variability and the lack of differentiation pose diagnostic challenges. We aim to further define the immunoprofile of this tumor. Methods and results: We reviewed the clinical history and performed immunohistochemistry for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, SOX2, SOX10, S100, histone H3 trimethylated on lysine 27 (H3K27me3), desmin, myogenin, CD99, epithelial membrane antigen (EMA) and transducin-like enhancer of split 1 (TLE1) on six primary intracranial sarcomas, DICER1-mutant, with appropriate controls. Targeted exome sequencing was performed on all cases. The sarcomas showed diffuse (n = 4), mosaic (n = 1) or minimal (≤5%, n = 1) loss of H3K27 trimethylation and nuclear TLE1 expression (n = 6). Four had immunohistochemical evidence of myogenic differentiation. SOX2, SOX10, S100 and EMA were negative; CD99 expression ranged from focal cytoplasmic (n = 4) to crisp diffuse membranous (n = 2). One tumour had focal cartilaginous differentiation. Similar immunohistochemical findings were observed in a pleuropulmonary blastoma (albeit with focal TLE1 expression), a DICER1-related pineoblastoma, and an embryonal tumour with a multilayered rosette-like DICER1-related cerebellar tumour. Targeted exome sequencing confirmed the presence of pathogenic biallelic DICER1 mutations in all tumours included in this study. Conclusion: We conclude that H3K27me3 and TLE1 immunostains, when utilised in combination, can be helpful diagnostic markers for primary intracranial sarcoma, DICER1-mutant.

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Section: Discussionmentioning

confidence: 99%

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin‐like enhancer 1 in primary intracranial sarcoma, DICER1‐mutant

Alexandrescu¹,

Meredith

Lidov³

et al. 2020

Histopathology

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“…In particular, TLE1 exhibits antineurogenic activity in mammalian forebrain development [21]. TLE1 is involved in diverse signaling pathways and has important roles in neurogenesis, sex determination, and segmentation during development [22]. Previous studies suggest TLE1 could be used as a diagnostic marker and is a possible therapeutic target in various malignancies.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed miRNAs and mRNAs in Vestibular Schwannoma by Integrated Analysis

Yan

Guo

et al. 2019

BioMed Research International

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Background. Vestibular schwannoma (VS) is benign, slow-growing brain tumor that negatively impacts patient quality of life, which may cause even death. This study aimed to explore key genes and microRNAs (miRNAs) associated with VS. Methods. The mRNA and miRNA expression profiles of VS downloaded from Gene Expression Omnibus (GEO) database were included in this study to perform an integrated analysis. The differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) were identified. Then, functional annotation and protein-protein interaction networks (PPI) of DEmRNAs were constructed. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Results. A total of 2627 DEmRNAs (1194 upregulated and 1433 downregulated DEmRNAs) and 21 DEmiRNAs (12 upregulated and 9 downregulated DEmiRNAs) were identified. ISG15, TLE1, and XPC were three hub proteins of VS-specific PPI network. A total of 2970 DEmiRNAs-DEmRNAs pairs were obtained. Among which, hsa-miR-181a-5p, hsa-miR-106-5p, and hsa-miR-34a-5p were the top three DEmiRNAs that covered most DEmRNAs. The functional annotation of DEmiRNA-target DEmRNAs revealed that the DEmiRNA-target DEmRNAs were significantly enriched in cGMP-PKG signaling pathway, adrenergic signaling in cardiomyocytes, and pathways in cancer. Conclusion. The results of this present study may provide a comprehensive understanding for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of VS and developing potential biomarkers of VS.

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“…In the healthy brain, FOXG1 represses gene expression, at least in part, by forming transcription complexes with Groucho/transducin‐like Enhancer of split (TLE) proteins (Marcal et al ., ; Roth et al ., ; Yao et al ., ). TLE family members are general transcriptional corepressors involved in controlling a variety of cellular processes, including the regulation of cell proliferation and differentiation (Buscarlet and Stifani, ; Turki‐Judeh and Courey, ; Yuan et al ., ). There are four full‐length TLE family members in mammals, named TLE1‐4, and two shorter isoforms, commonly referred to as Groucho‐related gene product (GRG) 5 and 6.…”

Section: Introductionmentioning

confidence: 97%

Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma‐initiating cells

et al. 2018

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Glioblastoma (GBM) is the most common and deadly malignant brain cancer of glial cell origin, with a median patient survival of less than 20 months. Transcription factors FOXG1 and TLE1 promote GBM propagation by supporting maintenance of brain tumour‐initiating cells (BTICs) with stem‐like properties. Here, we characterize FOXG1 and TLE1 target genes in GBM patient‐derived BTICs using ChIP‐Seq and RNA‐Seq approaches. These studies identify 150 direct FOXG1 targets, several of which are also TLE1 targets, involved in cell proliferation, differentiation, survival, chemotaxis and angiogenesis. Negative regulators of NOTCH signalling, including CHAC1, are among the transcriptional repression targets of FOXG1:TLE1 complexes, suggesting a crosstalk between FOXG1:TLE1 and NOTCH‐mediated pathways in GBM. These results provide previously unavailable insight into the transcriptional programs underlying the tumour‐promoting functions of FOXG1:TLE1 in GBM.

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TLE1 function and therapeutic potential in cancer

Cited by 22 publications

References 51 publications

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin‐like enhancer 1 in primary intracranial sarcoma, DICER1‐mutant

Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin‐like enhancer 1 in primary intracranial sarcoma, DICER1‐mutant

Identification of Differentially Expressed miRNAs and mRNAs in Vestibular Schwannoma by Integrated Analysis

Characterization of a FOXG1:TLE1 transcriptional network in glioblastoma‐initiating cells

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