RNA m1A Methyltransferase TRMT6 Predicts Poorer Prognosis and Promotes Malignant Behavior in Glioma.

Beibei Wang,Zhihua Zhao,Lihua Niu,Zhengyang Wang

doi:10.3389/fmolb.2021.692130

Abstract

Background: Glioma is the most prevalent central nervous system tumor in humans, and its prognosis remains unsatisfactory due to a lack of effective therapeutic targets. The ectopic expression of N1-methyladenosine (m1A) regulators is a key participant in tumorigenesis and progression. However, the m1A regulator expression status, prognostic value, and relationship with tumor clinical features in glioma remain unclear.Methods: Public datasets were used to analyze the mRNA and protein expression levels of m1A regulators. Kaplan–Meier and Cox regression analyses were performed to confirm the prognostic value of m1A regulators in glioma. Cellular experiments were conducted to verify the effect of TRMT6 on cell function. A comprehensive bioinformatics analysis was conducted to identify the potential molecular mechanisms regulated by TEMT6 in glioma.Results: We found that the dysregulation of m1A regulators was closely associated with tumorigenesis and progression in glioma. Furthermore, TRMT6 might be a powerful and independent biomarker for prognosis in glioma. Our study showed that inhibition of TRMT6 suppressed the proliferation, migration, and invasion of glioma cells. Mechanistically, TRMT6 may be involved in glioma progression by regulating cell cycle, PI3K-AKT, TGF-beta, MTORC1, NOTCH, and MYC pathways.Conclusions: Variation in m1A regulators was closely associated with malignant progression in glioma. Silencing TRMT6 suppressed the cell proliferation, migration, and invasion in glioma. m1A regulators, especially TRMT6, might play an essential role in the malignant progression of glioma.

Highlights

Glioma is the most common central nervous system tumor in humans, accounting for ∼40% of all brain cancers (Dawson and Kouzarides, 2012; Gusyatiner and Hegi, 2018)
Further studies indicate that m1A plays a crucial role in various cellular processes by regulating RNA stability and translation (Zhao et al, 2017; Xiong et al, 2018). m1A methylation involves a series of enzymes which are categorized into three types: m1A methyltransferases called “writer” (TRMT10C, TRMT61B, TRMT6, and TRMT61A), “‘eraser” are demethylases including ALKBH1 and ALKBH3, and m1A is recognized by m1A-binding protein, and they are jargonized as “reader” (YTHDF1, YTHDF2, YTHDF3, and YTHDC1) (Chujo and Suzuki, 2012; Safra et al, 2017; Dai et al, 2018; Chen et al, 2019)
To investigate the role of m1A modifications in tumor occurrence and progression for glioma, we systematically analyzed the relationship between the expression of m1A regulators and the clinical features in gliomas, such as WHO grades, 1p19q codeletion, and IDH mutant status according to TCGA and CGGA datasets

Summary

Introduction

Glioma is the most common central nervous system tumor in humans, accounting for ∼40% of all brain cancers (Dawson and Kouzarides, 2012; Gusyatiner and Hegi, 2018). Recent studies have shown that RNA methylation plays an important role in the determination of cell fate decisions, cell cycle regulation, and cancer development (Gilbert et al, 2016; Zhao et al, 2017; Huang et al, 2020). This indicates that RNA methylation might be a novel and potential therapeutic target for exploration. The m1A regulator expression status, prognostic value, and relationship with tumor clinical features in glioma remain unclear

Methods

Results

Conclusion