{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339333/"]},"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=GSE339333"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CHI3L1 regulates gene methylation modifications in ovarian cancer cells","description":"Adipocyte-tumor interaction plays a critical role in tumor microenvironment. Typically, high-grade serous ovarian carcinoma (HGSOC) preferentially metastasizes to the omentum, an adipocyte-rich tissue, and obesity correlates with worse patient prognosis. However, the underlying mechanisms remain poorly understood. Here, we identify a bidirectional adipocyte–cancer cell axis in which HGSOC cells stimulate lactate metabolism in adjacent adipocytes, leading to hypoxia-inducible factor 1α (HIF-1α) activation and subsequent secretion of chitinase 3-like 1 (CHI3L1). On the one hand, CHI3L1 acts as an inflammatory factor that promotes the secretion of additional cytokines, perpetuating omental inflammation, driving CD8⁺ T cell exhaustion, and shaping an immunosuppressive microenvironment that favors tumor metastasis. On the other hand, CHI3L1 binds to and stabilizes protein arginine methyltransferase 5 (PRMT5) in tumor cells, thereby enhancing its methyltransferase activity. This upregulation suppresses dual-specificity phosphatase 1 (DUSP1), a phosphatase of mitogen-activated protein kinase (MAPK), and sustains oncogenic MAPK signaling across multiple tumor models. Obesity amplifies this pathway by heightening HIF-1α activity and elevating CHI3L1 levels in adipose tissue, which drives both tumor progression and resistance to anti-angiogenic therapy. Pharmacological inhibition of CHI3L1 disrupts this signaling loop and restores therapeutic sensitivity, while also alleviating immune exhaustion in the tumor microenvironment. Collectively, our findings establish CHI3L1 as a key mediator of a unified mechanism that drives omental tropism and obesity-associated aggressive phenotypes, highlighting its potential as a prognostic biomarker and therapeutic target to improve anti-angiogenic therapy.","dates":{"publication":"2026/07/26"},"accession":"GSE339333","cross_references":{"GSM":["GSM9893683","GSM9893686","GSM9893684","GSM9893685"],"GPL":["34284"],"GSE":["339333"],"taxon":["Homo sapiens"]}}