{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:06:35Z","timestamp":1772118395550,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/11\/IYBA\/2018\/08"],"award-info":[{"award-number":["BT\/11\/IYBA\/2018\/08"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["21701017"],"award-info":[{"award-number":["21701017"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["NCD\/Ad\u2010hoc\/224\/2022\u201023"],"award-info":[{"award-number":["NCD\/Ad\u2010hoc\/224\/2022\u201023"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The emergence of constitutively active androgen receptor (AR) splice variant AR\u2010V7 poses a formidable challenge in treating prostate cancer, as it lacks the ligand binding region targeted by androgen\u2010deprivation therapies such as enzalutamide and abiraterone. AR\u2010V7 is critical for castration\u2010resistant prostate cancer (CRPC) development and progression; however, the molecular mechanisms regulating its expression and biological function remain poorly understood. Here, we investigate the role of IGF2BP2 in regulating AR\u2010V7 expression and CRPC progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To determine the clinical relevance of IGF2BP2 in CRPC, we analyzed the mRNA expression data for prostate cancer patients available in the Genomic Data Commons (GDC) Data Portal and cBioPortal. Next to investigate the role of IGF2BP2 in regulating AR\u2010V7 expression and enzalutamide resistance, we performed shRNA\u2010mediated IGF2BP2 knockdown and overexpression experiments followed by qRT\u2010PCR, immunoblot, colony\u2010formation, and MTT assays. Finally, we performed RIP\u2010qPCR, actinomycin\u2010D, and IGF2BP2 domain\u2010deletion analysis to study the mechanism by which IGF2BP2 regulates AR\u2010V7 stability, expression, and enzalutamide resistance in CRPC cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis revealed that IGF2BP2 is upregulated in CRPC patients and its expression positively correlates with increasing Gleason score in patients with CRPC. We demonstrate that IGF2BP2 silencing leads to downregulation of AR\u2010V7 and its downstream target genes without affecting AR levels. Additionally, IGF2BP2 knockdown also enhances the sensitivity of CRPC cells to enzalutamide while overexpression increases AR\u2010V7 expression and confers increased resistance to enzalutamide. Mechanistically, our experiments demonstrate that IGF2BP2 binds to the intronic splicing enhancer (ISE) region of AR\u2010V7, thereby enhancing its mRNA stability. Furthermore, our domain\u2010deletion analysis pinpoints the role of KH3 and KH4 domains of IGF2BP2 in regulating AR\u2010V7 stability and enzalutamide resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR\u2010V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70096","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T23:45:51Z","timestamp":1739490351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Insulin\u2010Like Growth Factor 2\n                    <scp>mRNA<\/scp>\n                    \u2010Binding Protein 2 (\n                    <scp>IGF2BP2<\/scp>\n                    ) Promotes Castration\u2010Resistant Prostate Cancer Progression by Regulating\n                    <scp>AR<\/scp>\n                    \u2010\n                    <scp>V7 mRNA<\/scp>\n                    Stability"],"prefix":"10.1002","volume":"8","author":[{"given":"Taruna","family":"Saini","sequence":"first","affiliation":[{"name":"Department of Biotechnology Indian Institute of Technology Hyderabad  Kandi Sangareddy India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devesh","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Indian Institute of Technology Hyderabad  Kandi Sangareddy India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajnikant","family":"Raut","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Indian Institute of Technology Hyderabad  Kandi Sangareddy 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