Thumbnail Image
Item

Musashi-2 (MSI2) regulation of DNA damage response in lung cancer

Bychov, Igor
; 
Deneka, Alexander Y.
; 
Topchu, Iuliia
; 
Pangeni, Rajendra P.
; 
Lengner, Christopher
; 
Karanicolas, John
; ; 
Makhov, Petr
; 
Boumber, Yanis
Citations
Altmetric:
Genre
Pre-print
Date
2023-06-14
Advisor
Committee member
Group
Fox Chase Cancer Center (Temple University)
Department
Cancer and Cellular Biology
Subject
Permanent link to this record
http://hdl.handle.net/20.500.12613/9229
Collections
Faculty/Researcher Works
Show all metadata
Files
Thumbnail Image
GolemisEtAl-PrePrint-2023-06.pdf
Adobe PDF, 6.4 MB
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.1101/2023.06.13.544756
Abstract
Lung 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.
Description
Citation
Bychov 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.
Citation to related work
bioRxiv
Has part
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
Embedded videos