{"doi":"10.1016/j.celrep.2024.115171","title":"miR-449a/miR-340 reprogram cell identity and metabolism in fusion-negative rhabdomyosarcoma","abstract":"Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, arises in skeletal muscle and remains in an undifferentiated state due to transcriptional and post-transcriptional regulators. Among its subtypes, fusion-negative RMS (FN-RMS) accounts for the majority of diagnoses in the pediatric population. MicroRNAs (miRNAs) are non-coding RNAs that modulate cell identity via post-transcriptional regulation of messenger RNAs (mRNAs). In this study, we identify miRNAs impacting FN-RMS cell identity, revealing miR-449a and miR-340 as major regulators of the cell cycle and p53 signaling. Through miR-eCLIP technology, we demonstrate that miR-449a and miR-340 directly target transcripts involved in glycolysis and mitochondrial pyruvate transport, inhibiting the mitochondrial pyruvate carrier (MPC) complex. Pharmacological MPC inhibition induces a similar metabolic shift, reducing metastatic potential and leading to cell cycle exit. Overall, miR-449 and miR-340 orchestrate FN-RMS cell identity, positioning MPC inhibition as a strategy to shift FN-RMS cells toward a non-tumorigenic, quiescent state.","journal":"Cell Reports","year":2025,"id":540062,"datarank":0.1708658134391438,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0060739701389273554,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0060739701389273554,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE276201"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1427504,"name":"Laura Yedigaryan","orcid":"0000-0002-1701-9109","position":1,"is_corresponding":false},{"id":731212,"name":"Nefele Giarratana","orcid":"0000-0002-8143-6230","position":2,"is_corresponding":false},{"id":1427950,"name":"Chao-chi Wang","orcid":null,"position":3,"is_corresponding":false},{"id":1427951,"name":"Gabriel Miró Garrido","orcid":null,"position":4,"is_corresponding":false},{"id":1427952,"name":"Ewoud Degreef","orcid":null,"position":5,"is_corresponding":false},{"id":1427505,"name":"Vittoria Marini","orcid":"0000-0002-0504-8682","position":6,"is_corresponding":false},{"id":51547,"name":"Gianmarco Rinaldi","orcid":"0000-0001-5191-4580","position":7,"is_corresponding":false},{"id":1332534,"name":"Bernard K. van der Veer","orcid":"0000-0002-2576-7529","position":8,"is_corresponding":false},{"id":1398072,"name":"Gabriele Sassi","orcid":"0000-0002-7921-2764","position":9,"is_corresponding":false},{"id":842344,"name":"Guy Eelen","orcid":"0000-0003-3354-5819","position":10,"is_corresponding":false},{"id":273620,"name":"Mélanie Planque","orcid":"0000-0001-7052-7084","position":11,"is_corresponding":false},{"id":1427506,"name":"Alessandro Fanzani","orcid":"0000-0001-7475-2668","position":12,"is_corresponding":false},{"id":1332539,"name":"Kian Peng Koh","orcid":"0000-0003-2523-5175","position":13,"is_corresponding":false},{"id":287648,"name":"Peter Carmeliet","orcid":"0000-0001-7961-1821","position":14,"is_corresponding":false},{"id":403028,"name":"Jason T. Yustein","orcid":"0000-0002-2052-0527","position":15,"is_corresponding":false},{"id":109854,"name":"Sarah‐Maria Fendt","orcid":"0000-0001-6018-9296","position":16,"is_corresponding":false},{"id":525348,"name":"Anne Uyttebroeck","orcid":"0000-0001-5644-424X","position":17,"is_corresponding":false},{"id":558907,"name":"Maurilio Sampaolesi","orcid":"0000-0002-2422-3757","position":18,"is_corresponding":false},{"id":820786,"name":"Enrico Pozzo","orcid":"0000-0002-3362-3509","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:52:34.520788Z","pmid":"39799567","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}