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EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression.

ABSTRACT: EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression.

PROVIDER: PRJNA1146484 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30193274_1.fastq.gz	Fastqsanger.gz
	SRR30193274_2.fastq.gz	Fastqsanger.gz
	SRR30193275_1.fastq.gz	Fastqsanger.gz
	SRR30193275_2.fastq.gz	Fastqsanger.gz
	SRR30193276_1.fastq.gz	Fastqsanger.gz

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EHMT1 mediates cellular motility in embryonal rhabdomyosarcoma by activating SOX8 expression.

Project description:In this study, we examined the role of EHMT1 in embryonal rhabdomyosarcoma (ERMS), the most frequent subtype of RMS. We report that EHMT1 plays a key role in the migratory and invasive capacity of ERMS cells in vitro and in vivo. Transcriptomic analysis of EHMT1-depleted cells revealed significant alteration in cell migration and invasion pathways. SOX8, a transcription factor that has key roles in cellular motility was significantly decreased upon EHMT1 loss. Consistently, SOX8 depletion phenotypically mimicked EHMT1 loss. Moreover, RNA-Sequencing of SOX8 depleted cells showed down regulation of several integrin genes. Mechanistically, we show that EHMT1 upregulates SOX8 via regulation of BRD4 expression, and consequently its occupancy at the promoter. Our study reveals a novel EHMT1-SOX8 axis that mediates metastasis in ERMS.

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Role of EHMT1 in Alveolar Rhabdomyosarcoma

Project description:Rhabdomyosarcoma (RMS) is a pediatric soft tissue sarcoma, wherein the malignant tumors arise from the myoblast like cells due to the perturbations in growth and differentiation. Alveolar rhabdomyosarcoma (ARMS) is one of the two major histological subtypes which exhibits high metastatic potential and tumor recurrence culminating in poor prognosis. In the recent past, understanding the epigenetic modifications in these tumors with less genetic alterations has shed light on the process of tumor pathogenesis and development of potential epi-drugs for the effective treatment strategies. Epigenetic regulator, Euchromatin histone lysine methyltransferase 1 (EHMT1)/G9A-like protein (GLP) and its homolog Euchromatin histone lysine methyltransferase 1 (EHMT2)/G9A has been shown to promote proliferation and inhibit differentiation in the mouse myoblast cells, independently. Also, previous study from our lab reported the overexpression of EHMT2 and molecular mechanism associated with the oncogenic phenotype in ARMS. However, expression pattern and functional role of EHMT1 in ARMS is unknown. Herein, we investigated the role of EHMT1 in ARMS. Our preliminary data indicated the overexpression of EHMT1 and the associated oncogenic phenotypes in ARMS. Although EHMT1 has shown to be upregulated and correlated with the increased disease severity in several cancers including gastric, esophagus, squamous cell carcinoma, ovarian and breast cancer, the mechanism involved in the EHMT1 mediated tumorigenesis was unclear. Therefore, through our current study we aimed to understand the expression pattern and the mechanism through which EHMT1 regulated cancer phenotypes in ARMS, for this we performed whole transcriptomic analysis in ARMS cell lines upon EHMT1 knockdown for the first time. In addition, we also compared the expression levels of EHMT1 between Human skeletal muscle myoblasts (HSMM) and ARMS patient samples (obtained from St Jude cloud database).

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Role of EHMT1 in Alveolar Rhabdomyosarcoma

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