GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE333nnn/GSE333837/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE333837GEOGSEfalsePhosphorylation-dependent regulation of gene expression and alternative splicing by THRAP3 in prostate cancerProstate 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.2026/08/25GSE333837GSM9775762GSM9775751GSM9775763GSM9775752GSM9775760GSM9775761GSM9775750GSM9775759GSM9775748GSM9775749GSM9775768GSM9775757GSM9775746GSM9775747GSM9775758GSM9775766GSM9775755GSM9775767GSM9775756GSM9775745GSM9775764GSM9775753GSM9775765GSM97757543428424676333837Homo sapiens