{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313017/"]},"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=GSE313017"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CHTOP Regulates ROS Homeostasis to Modulate Chemoresistance in Colorectal Cancer","description":"Chemotherapy resistance remains a significant challenge in colorectal cancer (CRC) treatment, with disrupted reactive oxygen species (ROS) homeostasis playing a central role. We identify CHTOP as a key regulator of ROS levels and chemoresistance in CRC. Mechanistically, CHTOP regulates ROS homeostasis by interacting with Nrf2 and modulating its SUMOylation via the SENP3-containing 5FMC complex. Notably, CHTOP expression is tightly controlled by a ROS-dependent feedback loop. The PSIP1/p52 isoform inhibits CHTOP expression by disrupting HNRNPH1-dependent splicing, leading to CHTOP degradation via nonsense-mediated decay (NMD). Meanwhile, ROS accumulation stabilizes SENP3, promoting the deSUMOylation and degradation of p52, thereby forming a ROS-SENP3-p52-CHTOP feedback loop. Thus, ROS levels both regulate and are regulated by CHTOP, maintaining redox balance. CHTOP downregulation in 5-FU-resistant CRC shifts cells into a higher-ROS steady state, which correlates with reduced 5-FU sensitivity. Both restoring CHTOP expression and inducing further depletion of CHTOP disrupt redox balance in 5-FU-resistant cells, reversing resistance and re-establishing sensitivity. These findings suggest that modulating CHTOP expression may offer a promising therapeutic strategy to overcome chemoresistance in CRC through redox regulation.","dates":{"publication":"2026/08/15"},"accession":"GSE313017","cross_references":{"GSM":["GSM9359218","GSM9359219","GSM9359220","GSM9359221","GSM9359222","GSM9359223"],"GPL":["34284"],"GSE":["313017"],"taxon":["Homo sapiens"]}}