12‐O‐tetradecanoylphorbol‐13‐acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells

Marchesi, Irene; Sanna, Luca; Fais, Milena; Fiorentino, Francesco Paolo; Giordano, Antonio; Bagella, Luigi

doi:10.1002/jcp.26107

Cited by 15 publications

(13 citation statements)

References 30 publications

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“…EZH2 expression can be induced by the fusion gene of EWS/FLI1 via binding to its promoter in Ewing sarcoma in vivo 11 . It was also demonstrated that EZH2 was aberrantly overexpressed in RMS primary tumors and cell lines, and downregulation of it in vitro can lead to muscle-like differentiation of RMS cells 12 – 14 . Some studies exist on synovial sarcoma revealed that EZH2 expressed in 76% of patients 15 .…”

Section: Introductionmentioning

confidence: 98%

High expression of EZH2 as a marker for the differential diagnosis of malignant and benign myogenic tumors

Zhang

Zeng

et al. 2018

Sci Rep

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Overlap in morphologic features between malignant and benign myogenic tumors, such as leiomyosarcoma (LMS) vs. leiomyoma as well as rhabdomyosarcoma (RMS) vs. rhabdomyoma, often makes differential diagnosis difficult and challenging. Here the expressions of Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste 12 (SUZ12), retinoblastoma protein associated protein 46 (RbAp46), Embryonic Ectoderm Development (EED) and ki-67 protein were detected by immunohistochemistry to evaluate their values in differential diagnosis. The expression of EZH2 mRNA was investigated by analyzing the Gene Expression Omnibus Datasets. The results demonstrated that EZH2 protein was detected in 81.25% (26/32) of LMS and 70.58% (36/51) of RMS, whereas none of leiomyoma (n = 16), rhabdomyoma (n = 15) and normal tissues (n = 31) showed positive immunostaining (p < 0.05). EZH2 protein was found to have a sensitivity of 91.30% and specificity of 100% in distinguishing well-differentiated LMS from cellular leiomyoma, and a sensitivity of 92.86% and specificity of 100% in distinguishing well-differentiated embryonal rhabdomyosarcoma (ERMS) from fetal rhabdomyoma. Besides, the expression of EZH2 mRNA was higher in LMS and RMS than in benign tumors (p < 0.05). The expressions of SUZ12 and RbAp46 protein were higher in RMS than in rhabdomyoma (p < 0.05). Conclusively, the high expression of EZH2 is a promising marker in distinguishing well–differentiated LMS from cellular leiomyoma, or well–differentiated ERMS from fetal rhabdomyoma, and the upregulation of EZH2 protein expression may occur at transcriptional level.

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Section: Introductionmentioning

confidence: 98%

High expression of EZH2 as a marker for the differential diagnosis of malignant and benign myogenic tumors

Zhang

Zeng

et al. 2018

Sci Rep

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“…With the emergence of high-throughput screening and combinatorial chemistry, the development of novel anticancer drugs increased dramatically. However, chemotherapeutic drugs often lead Several drugs used to treat cancer focus on the topic of epigenetics, which studies the changes of chromatin and, in specific, its ability to influence gene expression (Marchesi et al, 2017;Sanna et al, 2018). Drug discovery and target selection are intricate, uncertain, and expensive processes.…”

Section: Discussionmentioning

confidence: 99%

Target identification of a novel unsymmetrical 1,3,4‐oxadiazole derivative with antiproliferative properties

Lyu

Sanna

Bordoni

et al. 2020

Journal Cellular Physiology

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1,3,4‐Oxadiazole derivatives are widely used in research on antineoplastic drugs. Recently, we discovered a novel unsymmetrical 1,3,4‐oxadiazole compound with antiproliferative properties called 2j. To further investigate its possible targets and molecular mechanisms, RNA‐seq was performed and the differentially expressed genes (DEGs) were obtained after treatment. Data were analyzed using functional (Gene Ontology term) and pathway (Kyoto Encyclopedia of Genes and Genomes) enrichment of the DEGs. The hub genes were determined by the analysis of protein‐protein interaction networks. The connectivity map (CMap) information provided insight into the model action of antitumor small molecule drugs. Hub genes have been identified through function gene networks using STRING analysis. The small molecular targets obtained by CMap comparison showed that 2j is a tubulin inhibitor and it acts mainly affecting tumor cells through the cell cycle, FoxO signaling pathway, apoptotic, and p53 signaling pathways. The possible targets of 2j could be TUBA1A and TUBA4A. Molecular docking results indicated that 2j interacts at the colchicine‐binding site on tubulin.

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“…In a phase 2 clinical trial involving 33 SS patients with confirmed either SMARCB1 loss/depletion or SS18-SSX translocation and median of 2 preceding systemic treatments, single agent tazemetostat treatment resulted in stable disease in 11 patients with only 5 of those having stable disease lasting 16 weeks or more. No objective responses in pre-treated patients were seen [47] .…”

Section: Synovial Sarcomamentioning

confidence: 91%

Targeting EZH2 for the treatment of soft tissue sarcomas

Karolak¹,

Tracy²,

Shipley³

et al. 2021

JCMT

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Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis. Standard treatments for STS largely constitute tumour resection with chemotherapy and/or radiotherapy, and there has been little significant advancement in the application of novel therapies for treatment of these tumours. The current multimodal approach to therapy often leads to long-term side effects, and for some patients, resistance to cytotoxic agents is associated with local recurrence and/or metastasis. There is, therefore, a need for novel therapeutic strategies for the treatment of STS. Recent advances in epigenetics have implicated the histone methyltransferase, EZH2, in the development and progression of diseases such as breast cancer, lymphoma and more recently STS. Here we will review the current literature for EZH2 in STS, including high expression of EZH2 in STS and correlation of this with specific features of malignancy (metastasis, histological grade, and prognosis). The effects of targeting EZH2 using RNA interference and small molecule inhibitors will also be reviewed and the potential for the use of EZH2 inhibition in therapeutic strategies for STS patients will be discussed.

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12‐O‐tetradecanoylphorbol‐13‐acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells

Cited by 15 publications

References 30 publications

High expression of EZH2 as a marker for the differential diagnosis of malignant and benign myogenic tumors

High expression of EZH2 as a marker for the differential diagnosis of malignant and benign myogenic tumors

Target identification of a novel unsymmetrical 1,3,4‐oxadiazole derivative with antiproliferative properties

Targeting EZH2 for the treatment of soft tissue sarcomas

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