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

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.

Four types of RNA modification writers predict the prognosis of prostate cancer

“…These results suggest that RNA modification writers affect the development of PCa mainly by participating in cell cycle regulation. This is consistent with the results of previous studies (Liu et al, 2020; Wang et al, 2020; Wang, Niu, et al, 2021). Further univariate and multivariate Cox analyses were performed for risk scores and clinical factors (age, stage and lymph node metastasis), indicating that the risk model of RNA modification writers might be an independent prognostic factor for PCa.…”

TRMT6 is Suppressed by miR-191-5p and Functions as a Tumor Promoter in Ovarian Cancer

“…Recent research has shown that modi cation of m1A methylation plays an important role in the prognosis of OV and in shaping the immune microenvironment (34). TRMT6, a member of the tRNA methyltransferase family, is involved in post-translational modi cations, producing modi ed nucleoside m1A in tRNA, which acts as a writer (35). Zhao et al have shown that silencing TRMT6 inhibits cell proliferation, migration, and invasion in glioma (36).…”

Roles of RNA Modifications in Diverse Cellular Functions

“…Many studies have found positive associations with m 1 A regulators, such as the m 1 A methyltransferase TRMT6, and cancer ( Wang et al, 2019 ; Shi et al, 2020 ; Wang B. et al, 2021 ). However, few studies have established the biological mechanisms by which m 1 A regulators assert their oncogenic function.…”

“…However, few studies have established the biological mechanisms by which m 1 A regulators assert their oncogenic function. Inhibition of Trmt6 resulted in decreased proliferation in glioma cell lines, establishing a potential oncogenic role for TRMT6 in regulating proliferation ( Macari et al, 2016 ; Wang B. et al, 2021 ). Furthermore, inhibition of Alkbh3 , an m 1 A demethylase, resulted in decreased proliferation in HeLa, PANC-1, and NSCLC cancer cells, suggesting a potential role for this demethylase in proliferation ( Tasaki et al, 2011 ; Ueda et al, 2017 ; Chen et al, 2019 ).…”