{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["35(2)"],"submitter":["Li Y"],"funding":["National Science Foundation"],"pubmed_abstract":["Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NGFI-A-binding protein 2 (NAB2) and signal transducer and activator protein 6 (STAT6) genes on chromosome 12, wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies. Indeed, our <i>in vitro</i> studies show the STAT6 3' untranslated region (UTR)-targeting ASO (ASO 993523) was able to reduce expression of NAB2-STAT6 fusion transcripts in multiple SFT cell models with high efficiency (half-maximal inhibitory concentration: 116-300 nM). Encouragingly, <i>in vivo</i> treatment of SFT patient-derived xenograft mouse models with ASO 993523 resulted in acceptable tolerability profiles, reduced expression of NAB2-STAT6 fusion transcripts in xenograft tissues (21.9%), and, importantly, reduced tumor growth (32.4% decrease in tumor volume compared with the untreated control). Taken together, our study established ASO 993523 as a potential agent for the treatment of SFTs."],"journal":["Molecular therapy. Nucleic acids"],"pagination":["102154"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10950871"],"repository":["biostudies-literature"],"pubmed_title":["STAT6-targeting antisense oligonucleotides against solitary fibrous tumor."],"pmcid":["PMC10950871"],"pubmed_authors":["Tolentino A","Moura DS","Hayenga HN","Nguyen JT","Ramos R","Di Lernia D","Li Y","Tran N","Bleris L","Revenko AS","Martin-Broto J","Mondaza-Hernandez JL","Merino-Garcia J","Meyer CA"],"additional_accession":[]},"is_claimable":false,"name":"STAT6-targeting antisense oligonucleotides against solitary fibrous tumor.","description":"Solitary fibrous tumor (SFT) is a rare, non-hereditary soft tissue sarcoma thought to originate from fibroblastic mesenchymal stem cells. The etiology of SFT is thought to be due to an environmental intrachromosomal gene fusion between NGFI-A-binding protein 2 (NAB2) and signal transducer and activator protein 6 (STAT6) genes on chromosome 12, wherein the activation domain of STAT6 is fused with the DNA-binding domain of NAB2 resulting in the oncogenesis of SFT. All NAB2-STAT6 fusion variations discovered in SFTs contain the C-terminal of STAT6 transcript, and thus can serve as target site for antisense oligonucleotides (ASOs)-based therapies. Indeed, our <i>in vitro</i> studies show the STAT6 3' untranslated region (UTR)-targeting ASO (ASO 993523) was able to reduce expression of NAB2-STAT6 fusion transcripts in multiple SFT cell models with high efficiency (half-maximal inhibitory concentration: 116-300 nM). Encouragingly, <i>in vivo</i> treatment of SFT patient-derived xenograft mouse models with ASO 993523 resulted in acceptable tolerability profiles, reduced expression of NAB2-STAT6 fusion transcripts in xenograft tissues (21.9%), and, importantly, reduced tumor growth (32.4% decrease in tumor volume compared with the untreated control). Taken together, our study established ASO 993523 as a potential agent for the treatment of SFTs.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2026-06-26T03:29:15.336Z","creation":"2026-06-26T03:23:06.727Z"},"accession":"S-EPMC10950871","cross_references":{"pubmed":["38511173"],"doi":["10.1016/j.omtn.2024.102154"]}}