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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma

ABSTRACT: A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma

PROVIDER: PRJNA1155672 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30413900.fastq.gz	Fastqsanger.gz
	SRR30413901.fastq.gz	Fastqsanger.gz
	SRR30411908.fastq.gz	Fastqsanger.gz
	SRR30411909.fastq.gz	Fastqsanger.gz
	SRR30411910.fastq.gz	Fastqsanger.gz

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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma [Human_RNAseq_bulk]

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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma [bulk_ATACseq]

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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma [Mouse_RNAseq_bulk]

Project description:Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma occurring in the pediatric population, arises from the skeletal muscle compartment. Several transcriptional and post-transcriptional regulators lock the tumor in a continuous undifferentiated state and prevent the cells from returning to quiescence. MicroRNAs (miRNAs) are short non-coding RNAs that modulate cell identity by means of post-transcriptional regulation of messenger RNAs. In this study, we aimed at identifying miRNAs that could affect FN-RMS cell identity. Thus, we analyzed publicly available datasets and identified miR-449a and miR-340 as the main regulators of cell cycle and p53 signaling. Using miR-eCLIP technology, we identified the direct effects of miRNAs in FN-RMS cell lines, and an overall rewiring of cell identity at the transcriptomic, epigenetic and metabolic level. We observed that miR-449a+340 directly and indirectly targeted glycolysis and pyruvate entry into mitochondria by inhibiting mitochondrial pyruvate complex (MPC) inhibition. The pharmacological inhibition of MPC resulted in a similar metabolic shift with cell cycle exit and a significant reduction in metastatic potential of FN-RMS models. In conclusion, the combination of miR-449 and miR-340 play a pivotal role in orchestrating the cell identity of FN-RMS, and the modulation of MPC emerges as a key factor in redirecting FN-RMS towards a quiescent, non-tumorigenic state.

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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma [Human_RNAseq_bulk]

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Expression Profiling of human Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

Project description:Genome-wide gene expression in 33 fusion-positive and 25 fusion-negative rhabdomyosarcoma cases was studied using GeneChip Human Genome U133 Plus2 (Affymetrix) Fusion-positive versus fusion-negative rhabdomyosarcoma tumors

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Fusion Negative Rhabdomyosarcoma Cell Lines

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A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Expression Profiling of human Fusion-Positive and Fusion-Negative Rhabdomyosarcoma

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