{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293856/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293856"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Alphavirus M1 disrupts super-enhancer-driven oncogenic transcription in osteosarcoma [RNA-seq]","description":"Oncolytic virotherapy has shown promise for various cancers, but its application in osteosarcoma (OS) remains underexplored. This study provides the first evidence of the potent oncolytic activity of M1, a natural Getah-like alphavirus, against OS. We demonstrate that OS cells exhibit heightened sensitivity to M1 infection, with its anti-tumor effects not solely dependent on the canonical ER stress-induced apoptosis. Proteomic and ChIP-seq analyses show the DNA-directed RNA polymerase II subunit RPB1 contributes to oncogenic super-enhancer activity and serves as a direct target of M1-mediated regulation. The oncolytic potency correlated positively with the transcriptional dependency on RPB1 within super-enhancer regions. Mechanistically, the viral non-structural protein NSP2 disrupts super-enhancer activity by recruiting the CUL2-RBX1-ELOC complex, which triggers K63-linked ubiquitination and degradation of RPB1. These findings uncover a previously unrecognized oncolytic mechanism of M1 and its therapeutic potential in OS, with RPB1 as a predictive biomarker for virotherapy response.","dates":{"publication":"2026/05/31"},"accession":"GSE293856","cross_references":{"GSM":["GSM8891989","GSM8891988","GSM8891998","GSM8891976","GSM8891997","GSM8891975","GSM8891974","GSM8891996","GSM8891995","GSM8891973","GSM8891994","GSM8891972","GSM8891971","GSM8891993","GSM8891992","GSM8891991","GSM8892002","GSM8891990","GSM8892001","GSM8892000","GSM8891979","GSM8891978","GSM8891977","GSM8891999","GSM8891987","GSM8891986","GSM8891985","GSM8891984","GSM8891983","GSM8891982","GSM8891981","GSM8891980"],"GPL":["24676"],"GSE":["293856"],"taxon":["Homo sapiens"]}}