{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293855/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293855"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Alphavirus M1 disrupts super-enhancer-driven oncogenic transcription in osteosarcoma [ChIP-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":"GSE293855","cross_references":{"GSM":["GSM8891954","GSM8891953","GSM8891952","GSM8891951","GSM8891958","GSM8891957","GSM8891956","GSM8891955"],"GPL":["24676"],"GSE":["293855"],"taxon":["Homo sapiens"]}}