Academic Journal
CAMK2D: a novel molecular target for BAP1-deficient malignant mesothelioma
| العنوان: | CAMK2D: a novel molecular target for BAP1-deficient malignant mesothelioma |
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| المؤلفون: | Karnan, Sivasundaram, Ota, Akinobu, Murakami, Hideki, Rahman, Md. Lutfur, Wahiduzzaman, Md, Hasan, Muhammad Nazmul, Vu, Lam Quang, Hanamura, Ichiro, Inoko, Akihito, Riku, Miho, Ito, Hideaki, Kaneko, Yoshifumi, Hyodo, Toshinori, Konishi, Hiroyuki, Tsuzuki, Shinobu, Hosokawa, Yoshitaka |
| المساهمون: | MEXT | Japan Society for the Promotion of Science |
| المصدر: | Cell Death Discovery ; volume 9, issue 1 ; ISSN 2058-7716 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Malignant mesothelioma (MMe) is a rare but aggressive malignancy. Although the molecular genetics of MMe is known, including BRCA1-associated protein-1 ( BAP1 ) gene alterations, the prognosis of MMe patients remains poor. Here, we generated BAP1 knockout ( BAP1 -KO) human mesothelial cell clones to develop molecular-targeted therapeutics based on genetic alterations in MMe. cDNA microarray and quantitative RT-PCR (qRT-PCR) analyses revealed high expression of a calcium/calmodulin-dependent protein kinase type II subunit delta ( CAMK2D ) gene in the BAP1 -KO cells. CAMK2D was highly expressed in 70% of the human MMe tissues (56/80) and correlated with the loss of BAP1 expression, making it a potential diagnostic and therapeutic target for BAP1 -deficient MMe. We screened an anticancer drugs library using BAP1 -KO cells and successfully identified a CaMKII inhibitor, KN-93, which displayed a more potent and selective antiproliferative effect against BAP1 -deficient cells than cisplatin or pemetrexed. KN-93 significantly suppressed the tumor growth in mice xenografted with BAP1 -deficient MMe cells. This study is the first to provide a potential molecular-targeted therapeutic approach for BAP1- deficient MMe. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41420-023-01552-5 |
| الاتاحة: | http://dx.doi.org/10.1038/s41420-023-01552-5 https://www.nature.com/articles/s41420-023-01552-5.pdf https://www.nature.com/articles/s41420-023-01552-5 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.ADDF6794 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41420-023-01552-5 |
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