{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336635/"]},"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=GSE336635"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"tRNA dosage regulates lineage plasticity and therapy resistance in prostate cancer through codon bias [RNA-seq]","description":"Lineage plasticity underlies therapeutic resistance in cancer, yet the translational mechanisms enabling this phenotypic flexibility remain largely unknown. Using prostate cancer as a paradigm of lineage dependence, we performed unbiased small RNA sequencing and identified tRNAArg(UCU)-1 as a regulator of lineage transitions and therapy resistance. tRNAArg(UCU)-1 is both necessary and sufficient to reprogram lineage dependence which can be tuned to restore sensitivity to androgen receptor-targeted therapies. We identify TARDBP and ZSCAN29 as DNA-binding proteins that directly engage the genomic locus of tRNAArg(UCU)-1 to regulate its expression revealing the importance of non-canonical tRNA-specific gene regulation. Mechanistically, tRNAArg(UCU)-1 controls a translational program centered on SWI/SNF chromatin remodelers, which are necessary to maintain lineage fidelity. In patients, tRNAArg(UCU)-1 is downregulated in neuroendocrine prostate cancer and its loss is associated with accelerated metastasis and poor survival. These findings uncover a previously unrecognized tRNA-specific regulatory axis that links codon biology to lineage dependence and therapy resistance in prostate cancer.","dates":{"publication":"2026/08/26"},"accession":"GSE336635","cross_references":{"GSM":["GSM9839140","GSM9839145","GSM9839146","GSM9839147","GSM9839148","GSM9839141","GSM9839149","GSM9839150","GSM9839151","GSM9839156","GSM9839113","GSM9839157","GSM9839158","GSM9839114","GSM9839115","GSM9839159","GSM9839152","GSM9839153","GSM9839154","GSM9839155","GSM9839116","GSM9839117","GSM9839118","GSM9839119","GSM9839160","GSM9839161","GSM9839162","GSM9839123","GSM9839167","GSM9839124","GSM9839125","GSM9839126","GSM9839163","GSM9839164","GSM9839120","GSM9839121","GSM9839165","GSM9839166","GSM9839122","GSM9839127","GSM9839128","GSM9839129","GSM9839134","GSM9839135","GSM9839136","GSM9839137","GSM9839130","GSM9839131","GSM9839132","GSM9839133","GSM9839138","GSM9839139"],"GPL":["24676"],"GSE":["336635"],"taxon":["Homo sapiens"]}}