Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma

Abstract Objectives To investigate the regulation of the N‐6‐methyladenosine (m6A) methyltransferases METTL3, METTL14, WTAP, KIAA1429, and METTL4, referred to as “m6A writers,” in clear cell renal cell carcinoma (ccRCC), and other RCC subtypes in respect of the potential prognostic value. Patients a...

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Autores principales: Larissa Gundert, Alexander Strick, Felix vonHagen, Doris Schmidt, Niklas Klümper, Yuri Tolkach, Marieta Toma, Glen Kristiansen, Manuel Ritter, Jörg Ellinger
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Lenguaje:EN
Publicado: Wiley 2021
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Acceso en línea:https://doaj.org/article/4ca73d20926b4acb80b4b8068223207f
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spelling oai:doaj.org-article:4ca73d20926b4acb80b4b8068223207f2021-11-17T16:19:36ZSystematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma2688-452610.1002/bco2.89https://doaj.org/article/4ca73d20926b4acb80b4b8068223207f2021-11-01T00:00:00Zhttps://doi.org/10.1002/bco2.89https://doaj.org/toc/2688-4526Abstract Objectives To investigate the regulation of the N‐6‐methyladenosine (m6A) methyltransferases METTL3, METTL14, WTAP, KIAA1429, and METTL4, referred to as “m6A writers,” in clear cell renal cell carcinoma (ccRCC), and other RCC subtypes in respect of the potential prognostic value. Patients and methods Tissue samples were collected within the framework of the Biobank at the Center for Integrated Oncology Bonn. The expression of the methyltransferases was systematically determined in clear cell renal carcinoma (ccRCC) on the RNA (real‐time PCR) and protein level (immunohistochemistry). Additionally, protein expression of the m6A writers was further investigated in papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and normal renal tissue (immunohistochemistry). Results The expression of all m6A‐methyltransferases was significantly downregulated in ccRCC compared to benign renal tissue. Low m6A‐methyltransferase levels were correlated with higher histological grade, advanced pT‐stage, pN‐stage, and metastatic disease. Reduced m6A‐methyltransferase expression was associated with shorter overall survival. Conclusion In conclusion, m6A‐methyltransferases are dysregulated in ccRCC and might act as tumor suppressor genes, which could be of particular importance for future diagnostic and therapeutic options.Larissa GundertAlexander StrickFelix vonHagenDoris SchmidtNiklas KlümperYuri TolkachMarieta TomaGlen KristiansenManuel RitterJörg EllingerWileyarticleccRCCKIAA1429m6AMETTL3METTL14METTL4Diseases of the genitourinary system. UrologyRC870-923ENBJUI Compass, Vol 2, Iss 6, Pp 402-411 (2021)
institution DOAJ
collection DOAJ
language EN
topic ccRCC
KIAA1429
m6A
METTL3
METTL14
METTL4
Diseases of the genitourinary system. Urology
RC870-923
spellingShingle ccRCC
KIAA1429
m6A
METTL3
METTL14
METTL4
Diseases of the genitourinary system. Urology
RC870-923
Larissa Gundert
Alexander Strick
Felix vonHagen
Doris Schmidt
Niklas Klümper
Yuri Tolkach
Marieta Toma
Glen Kristiansen
Manuel Ritter
Jörg Ellinger
Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
description Abstract Objectives To investigate the regulation of the N‐6‐methyladenosine (m6A) methyltransferases METTL3, METTL14, WTAP, KIAA1429, and METTL4, referred to as “m6A writers,” in clear cell renal cell carcinoma (ccRCC), and other RCC subtypes in respect of the potential prognostic value. Patients and methods Tissue samples were collected within the framework of the Biobank at the Center for Integrated Oncology Bonn. The expression of the methyltransferases was systematically determined in clear cell renal carcinoma (ccRCC) on the RNA (real‐time PCR) and protein level (immunohistochemistry). Additionally, protein expression of the m6A writers was further investigated in papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and normal renal tissue (immunohistochemistry). Results The expression of all m6A‐methyltransferases was significantly downregulated in ccRCC compared to benign renal tissue. Low m6A‐methyltransferase levels were correlated with higher histological grade, advanced pT‐stage, pN‐stage, and metastatic disease. Reduced m6A‐methyltransferase expression was associated with shorter overall survival. Conclusion In conclusion, m6A‐methyltransferases are dysregulated in ccRCC and might act as tumor suppressor genes, which could be of particular importance for future diagnostic and therapeutic options.
format article
author Larissa Gundert
Alexander Strick
Felix vonHagen
Doris Schmidt
Niklas Klümper
Yuri Tolkach
Marieta Toma
Glen Kristiansen
Manuel Ritter
Jörg Ellinger
author_facet Larissa Gundert
Alexander Strick
Felix vonHagen
Doris Schmidt
Niklas Klümper
Yuri Tolkach
Marieta Toma
Glen Kristiansen
Manuel Ritter
Jörg Ellinger
author_sort Larissa Gundert
title Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
title_short Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
title_full Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
title_fullStr Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
title_full_unstemmed Systematic expression analysis of m6A RNA methyltransferases in clear cell renal cell carcinoma
title_sort systematic expression analysis of m6a rna methyltransferases in clear cell renal cell carcinoma
publisher Wiley
publishDate 2021
url https://doaj.org/article/4ca73d20926b4acb80b4b8068223207f
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