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 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.

Comprehensive Analysis of N6-Methyladenosine (m6A) Writers, Erasers, and Readers in Cervical Cancer

“…Research has implicated post-transcriptional messenger RNA (mRNA) modification to be involved in tumorigenesis, proliferation, angiogenesis, and tumor immunity across different cancer entities [9][10][11]. In this context, N6-methyladenosine (m6A) has been identified as the most common type of mRNA modification.…”

The role of RNA-modifying proteins in renal cell carcinoma

“…In contrast, METTL7A expression was considerably lower in renal cancer than in normal tissues, and its low expression was associated with poor prognosis [ 49 ]. METTL3 played a tumor-suppressive role in the RCC, and its downregulation was associated with larger tumor size, higher histological grade, and poor survival [ 50 , 51 ]. In RCC, WTAP was found to maintain the stability of CDK2 mRNA, which in turn promotes the proliferation of RCC cells [ 52 ].…”

Comprehensive immunohistochemical analysis of N6-methyladenosine (m6A) writers, erasers, and readers in endometrial cancer

“…In this context, there is increasing evidence for posttranscriptional RNA modification to be critically involved in tumorigenesis, progression, and genesis of therapy resistance—thereby representing an interesting candidate for both, therapeutical and diagnostic applications (Strick et al 2020 ; Gundert et al 2021 ; Hagen et al 2021 ). N6-methyladenosine (m6A) is the most abundant messenger RNA (mRNA) modification.…”