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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.

SUBMITTER: Wang B

PROVIDER: S-EPMC8493077 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHomeobox D11 (HOXD11) plays an important role in a variety of cancers, but its precise role in gliomas remains unclear. This study aimed to explore the relationship between HOXD11 and gliomas by combining bioinformatics methods with basic experimental validation.Materials and methodsObtain gene expression information and clinical information of glioma and non-tumor brain tissue samples from multiple public databases such as TCGA (666 glioma samples), CGGA (749 glioma samples), GEPIA(163 glioblastoma samples and 207 normal control samples), GEO (GSE4290 and GSE15824). Nine cases of glioma tissue and five cases of normal control brain tissue were collected from the clinical department of Henan Provincial People's Hospital for further verification. A series of bioinformatic analysis methods were used to confirm the relationship between HOXD11 expression and overall survival and clinical molecular characteristics of patients with glioma. RT-qPCR was used to verify the change of expression level of HOXD11 in glioma cells and tissues. MTT assay, colony formation assay, wound-healing assay, immunofluorescence staining, flow cytometry and western blotting were used to detect the effect of HOXD11 on the biological behavior of glioma cell line U251.ResultsThe high expression of HOXD11 was significantly related to age, World Health Organization (WHO) grade, chemotherapy status, histological type, and even 1p19q codeletion data and isocitrate dehydrogenase (IDH) mutation. HOXD11, as an independent risk factor, reduces the overall survival of glioma patients and has diagnostic value for the prognosis of glioma. Gene Set Enrichment Analysis (GSEA) showed that HOXD11 was significantly enriched in cell signaling pathway such as cell cycle, DNA replication and so on. Finally, we confirmed that the knockout of HOXD11 can inhibit the proliferation and invasion of U251 glioma cells, and change the biological behavior of tumor cells by preventing the progression of cell cycle.ConclusionsHOXD11 may be used as a candidate biomarker for the clinical application of targeted drug and prognostic assessment treatment of glioma. In addition, This study will help to explore the pathological mechanism of glioma.

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

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