SFPQ promotes RAS-mutant cancer cell growth by modulating 5'-UTR mediated translational control of CK1α.

Autor:	Kok VJT; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore., Tang JY; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore., Eng GWL; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore., Tan SY; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore., Chin JTF; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore., Quek CH; School of Applied Science, Temasek Polytechnic, Singapore., Lai WX; Department of Physiology, YLLSoM, National University of Singapore, Singapore., Lim TK; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore., Lin Q; Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore., Chua JJE; Department of Physiology, YLLSoM, National University of Singapore, Singapore.; LSI Neurobiology Programme, National University of Singapore, Singapore.; Healthy Longevity Translational Research Programme, YLLSoM, National University of Singapore, Singapore., Cheong JK; Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine (YLLSoM), National University of Singapore, Singapore.; NUS Centre for Cancer Research, National University of Singapore, Singapore.; Department of Biochemistry, YLLSoM, National University of Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	NAR cancer [NAR Cancer] 2022 Sep 27; Vol. 4 (3), pp. zcac027. Date of Electronic Publication: 2022 Sep 27 (Print Publication: 2022).
DOI:	10.1093/narcan/zcac027
Abstrakt:	Oncogenic mutations in the RAS family of small GTPases are commonly found in human cancers and they promote tumorigenesis by altering gene expression networks. We previously demonstrated that Casein Kinase 1α (CK1α), a member of the CK1 family of serine/threonine kinases, is post-transcriptionally upregulated by oncogenic RAS signaling. Here, we report that the CK1α mRNA contains an exceptionally long 5'-untranslated region (UTR) harbouring several translational control elements, implicating its involvement in translational regulation. We demonstrate that the CK1α 5'-UTR functions as an IRES element in HCT-116 colon cancer cells to promote cap-independent translation. Using tobramycin-affinity RNA-pulldown assays coupled with identification via mass spectrometry, we identified several CK1α 5'-UTR-binding proteins, including SFPQ. We show that RNA interference targeting SFPQ reduced CK1α protein abundance and partially blocked RAS-mutant colon cancer cell growth. Importantly, transcript and protein levels of SFPQ and other CK1α 5'-UTR-associated RNA-binding proteins (RBPs) are found to be elevated in early stages of RAS-mutant cancers, including colorectal and lung adenocarcinoma. Taken together, our study uncovers a previously unappreciated role of RBPs in promoting RAS-mutant cancer cell growth and their potential to serve as promising biomarkers as well as tractable therapeutic targets in cancers driven by oncogenic RAS. (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Cancer.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu