دورية أكاديمية
CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression
| العنوان: | CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression |
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| المؤلفون: | Cai, Huiqiang, Zhang, Bin, Ahrenfeldt, Johanne, Joseph, Justin V., Riedel, Maria, Gao, Zongliang, Thomsen, Sofie K., Christensen, Ditte S., Bak, Rasmus O., Hager, Henrik, Vendelbo, Mikkel H., Gao, Xin, Birkbak, Nicolai, Thomsen, Martin K. |
| المصدر: | Cai , H , Zhang , B , Ahrenfeldt , J , Joseph , J V , Riedel , M , Gao , Z , Thomsen , S K , Christensen , D S , Bak , R O , Hager , H , Vendelbo , M H , Gao , X , Birkbak , N & Thomsen , M K 2024 , ' CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression ' , Nature Communications , vol. 15 , no. 1 , 2088 . https://doi.org/10.1038/s41467-024-46370-0Test , https://doi.org/10.1038/s41467-024-46370-0Test |
| سنة النشر: | 2024 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | Male, Humans, Animals, Mice, CRISPR-Cas Systems/genetics, Prostatic Neoplasms/genetics, Transcriptome, Multigene Family |
| الوصف: | Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://pure.au.dk/portal/en/publications/48136e79-1998-4e13-986b-0c921f9b3f18Test |
| DOI: | 10.1038/s41467-024-46370-0 |
| الإتاحة: | https://doi.org/10.1038/s41467-024-46370-0Test https://pure.au.dk/portal/en/publications/48136e79-1998-4e13-986b-0c921f9b3f18Test http://www.scopus.com/inward/record.url?scp=85187165808&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.78832D3E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-46370-0 |
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