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| Status |
Public on Nov 27, 2024 |
| Title |
A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma [snRNAseq and scATACseq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Human fusion-negative rhabdomyosarcoma (FN-RMS) cell line RD18 was transfected with either lipofectamine or miR-449a + miR-340 for 60 hours, and subsequently single-nuclei multiomic RNAseq and ATACseq was performed
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| Contributor(s) |
Pozzo E, Sampaolesi M |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 22, 2024 |
| Last update date |
Nov 27, 2024 |
| Contact name |
Maurilio Sampaolesi |
| E-mail(s) |
[email protected]
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| Organization name |
KU Leuven
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| Department |
Department of Development and Regeneration
|
| Street address |
Herestraat 49, ON4 - box 804
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| City |
Leuven |
| ZIP/Postal code |
3000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE276201 |
A multitargeting approach rewires cell identity in fusion-negative rhabdomyosarcoma |
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| Relations |
| BioProject |
PRJNA1189452 |
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