{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333837/"]},"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=GSE333837"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Phosphorylation-dependent regulation of gene expression and alternative splicing by THRAP3 in prostate cancer","description":"Prostate cancer (CaP) is a leading cause of cancer deaths in American men. Searching for novel treatments, we uncovered a critical role for the poorly characterized mitotic citron kinase (CIT) in CaP growth and tumorigenicity. Thyroid Hormone Receptor-Associated Protein 3 (THRAP3) is an RNA-binding protein implicated in mRNA splicing, stability, and DNA damage response that our prior studies identified as a CIT substrate. THRAP3 silencing and overexpression diminished and increased, respectively, CaP cell proliferation, mimicking CIT’s effects. We then identified the several THRAP3-bound transcripts, one of which is CPT1A. CPT1A was found to be alternatively spliced by THRAP3 in prostate cancer cells generating a catalytically inactive, alternatively spliced variant, CPT1A-v2, while having no effect on the conventional active variant, CPT1A-v1. We demonstrate the therapeutic potential of disrupting the THRAP3-RNA binding via RNA decoys and antisense oligonucleotides (ASOs) which resulted in reduced synthesis of the oncogenic variant of CPT1A-v2 and thereby reduced growth of prostate cancer cells and patient-derived organoids (PDOs). In addition, overexpression of the oncogenic splice variant, CPT1A-v2 increased the prostate cancer cell growth, xenograft tumor volume and PDO growth, while CPT1A-v2 overexpression had either no or opposite effects. Targeting the synthesis of such variants by disrupting the THRAP3-RNA binding, therefore, may provide fresh therapeutic perspectives. These findings define a novel mechanism by which CIT rewires alternative splicing in CaP and present new therapeutic opportunities for targeting aggressive CaP.","dates":{"publication":"2026/08/25"},"accession":"GSE333837","cross_references":{"GSM":["GSM9775762","GSM9775751","GSM9775752","GSM9775763","GSM9775760","GSM9775761","GSM9775750","GSM9775759","GSM9775748","GSM9775749","GSM9775768","GSM9775757","GSM9775746","GSM9775747","GSM9775758","GSM9775755","GSM9775766","GSM9775767","GSM9775745","GSM9775756","GSM9775764","GSM9775753","GSM9775765","GSM9775754"],"GPL":["34284","24676"],"GSE":["333837"],"taxon":["Homo sapiens"]}}