von Hagen, Felix, Gundert, Larissa, Strick, Alexander, Klumper, Niklas, Schmidt, Doris, Kristiansen, Glen, Tolkach, Yuri, Toma, Marieta, Ritter, Manuel and Ellinger, Jorg (2021). N-6-Methyladenosine (m(6)A) readers are dysregulated in renal cell carcinoma. Mol. Carcinog., 60 (5). S. 354 - 363. HOBOKEN: WILEY. ISSN 1098-2744

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Abstract

N-6-Methyladenosine (m(6)A) is the most common modification of messenger RNA (mRNA) in mammals. It critically influences RNA metabolism and plays an essential role in virtually all types of bioprocesses including gene expression, tissue development, self-renewal and differentiation of stem cells, stress response and circadian clock control. It plays a crucial role in carcinogenesis and could be used as a prognostic and a diagnostic tool and as a target for new anticancer therapies. m(6)A modification is dynamically and reversibly regulated by three types of proteins. Methyltransferases, so-called writers add a methyl group to the adenosine, which can be removed by demethylases, also called erasers. m(6)A-specific RNA-binding proteins, from here on referred to as readers, preferentially bind to the m(6)A site and mediate biological functions, such as translation, splicing or decay of RNA. In this study, we examined the expression of the six m(6)A readers HNRNPA2B1, HNRNPC, YTHDC1 and YTHDF1-3 in clear cell renal carcinoma (ccRCC). We show that on mRNA level the expression of all six m(6)A readers is significantly downregulated compared to normal renal tissue and on protein level five out of six readers are dysregulated. Lower levels of some m(6)A readers are correlated with advanced stage and grade as well as associated with a shorter overall, progression-free and cancer-specific survival. In summary, we could show that m(6)A readers are dysregulated in ccRCC and might therefore act as a tumor marker, could give further information on the individual prognosis and be a target of innovative cancer therapy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
von Hagen, FelixUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gundert, LarissaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strick, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klumper, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, DorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristiansen, GlenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tolkach, YuriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toma, MarietaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ritter, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellinger, JorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-570775
DOI: 10.1002/mc.23297
Journal or Publication Title: Mol. Carcinog.
Volume: 60
Number: 5
Page Range: S. 354 - 363
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1098-2744
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Biochemistry & Molecular Biology; OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/57077

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