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dc.creatorBychov, Igor
dc.creatorDeneka, Alexander Y.
dc.creatorTopchu, Iuliia
dc.creatorPangeni, Rajendra P.
dc.creatorLengner, Christopher
dc.creatorKaranicolas, John
dc.creatorGolemis, Erica
dc.creatorMakhov, Petr
dc.creatorBoumber, Yanis
dc.date.accessioned2023-11-14T17:03:04Z
dc.date.available2023-11-14T17:03:04Z
dc.date.issued2023-06-14
dc.identifier.citationBychov I, Deneka AY, Topchu I, Pangeni RP, Lengner C, Karanicolas J, Golemis EA, Makhov P, Boumber Y. Musashi-2 (MSI2) regulation of DNA damage response in lung cancer [Preprint]. bioRxiv. 2023 Jun 14. doi:10.1101/2023.06.13.544756.
dc.identifier.urihttp://hdl.handle.net/20.500.12613/9229
dc.description.abstractLung cancer is one of the most common types of cancers worldwide. Non-small cell lung cancer (NSCLC), typically caused by KRAS and TP53 driver mutations, represents the majority of all new lung cancer diagnoses. Overexpression of the RNA-binding protein (RBP) Musashi-2 (MSI2) has been associated with NSCLC progression. To investigate the role of MSI2 in NSCLC development, we compared the tumorigenesis in mice with lung-specific Kras-activating mutation and Trp53 deletion, with and without Msi2 deletion (KP versus KPM2 mice). KPM2 mice showed decreased lung tumorigenesis in comparison with KP mice what supports published data. In addition, using cell lines from KP and KPM2 tumors, and human NSCLC cell lines, we found that MSI2 directly binds ATM/Atm mRNA and regulates its translation. MSI2 depletion impaired DNA damage response (DDR) signaling and sensitized human and murine NSCLC cells to treatment with PARP inhibitors in vitro and in vivo. Taken together, we conclude that MSI2 supports lung tumorigenesis, in part, by direct positive regulation of ATM protein expression and DDR. This adds the knowledge of MSI2 function in lung cancer development. Targeting MSI2 may be a promising strategy to treat lung cancer.
dc.format.extent24 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.isreferencedbybioRxiv
dc.rightsAll Rights Reserved
dc.titleMusashi-2 (MSI2) regulation of DNA damage response in lung cancer
dc.typeText
dc.type.genrePre-print
dc.contributor.groupFox Chase Cancer Center (Temple University)
dc.description.departmentCancer and Cellular Biology
dc.relation.doihttp://dx.doi.org/10.1101/2023.06.13.544756
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.creator.orcidGolemis|0000-0003-3618-3673
dc.temple.creatorDeneka, Alexander Y.
dc.temple.creatorKaranicolas, John
dc.temple.creatorGolemis, Erica A.
dc.temple.creatorMakhov, Petr
refterms.dateFOA2023-11-14T17:03:04Z


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