Genetic characteristics and prognostic implications of m1A regulators in pancreatic cancer

Niu

et al. 2021

Front. Mol. Biosci.

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.

Section: Discussionmentioning

confidence: 99%

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

Niu

et al. 2021

Front. Mol. Biosci.

Clinical Laboratory Analysis

“…14 The expression of m 5 C regulators is also linked to a variety of human cancers, 15,16 and m 1 A is considered important in the regulation of tumor development. [17][18][19] This study was designed to investigate the role of m 5 C and m 1 A regulators in CRC prognosis (using bioinformatics methods) and to analyze the association between these regulators and differences in survival as well as the clinicopathological characteristics and TIM in CRC tissues. Furthermore, this study helps to explore novel biomarkers that predict the therapeutic efficacy of current treatments and benefit therapeutic modulation.…”

Section: Introductionmentioning

confidence: 99%

Role of m⁵C RNA methylation regulators in colorectal cancer prognosis and immune microenvironment

Fang

Miao

Zeng

et al. 2022

Background RNA modification has become one of the hot topics of research as it can be used for tumor prognosis. However, its role in various biological processes is still poorly understood. The aim of this study was to investigate the role of m5C and m1A regulators on colorectal cancer prognosis using bioinformatics tools. The association between these regulators and differences in patient survival as well as the clinicopathological characteristics and tumor immune microenvironment in colorectal cancer tissues were assessed. Methods We selected publicly available colorectal cancer data sets from The Cancer Genome Atlas and used the “limma” package in R to identify differentially expressed genes. The least absolute shrinkage and selection operator regression model was used to calculate the prognostic risk, and a risk prediction model was constructed, to help assess the prognostic values of the differentially expressed genes. Finally, using TISCH and TIMER, we assessed the extent of cellular infiltration in colorectal cancer. Results We explored NSUN6 and DNMT3A expression using UALCAN and HPA and found that their expression is significantly increased in colorectal cancer tissues and correlated with sex and TP53 mutation status. Moreover, we found NSUN6 and DNMT3A were related to the infiltration of six major immune cells, with DNMT3A being closely related to dendritic cells, CD4+ T cells, and B cells, whereas NSUN6 to B cells and CD8+ T cells. Conclusion Our findings suggest that m5C regulators can predict the clinical prognostic risk and regulate the tumor immune microenvironment in colorectal cancer.

“…In pancreatic cancer, m1A regulator genetic variations are related to clinical stage, and CNVs are closely associated with the expression of m1A regulators. Notably, the expression level of ALKBH1 is closely associated with the prognosis of patients with pancreatic cancer ( 22 ). Li et al.…”

Section: Discussionmentioning

confidence: 99%

A Novel m1A-Score Model Correlated With the Immune Microenvironment Predicts Prognosis in Hepatocellular Carcinoma

2022

RNA methylation plays crucial roles in gene expression and has been indicated to be involved in tumorigenesis, while it is still unclear whether m1A modifications have potential roles in the prognosis of hepatocellular carcinoma (HCC). In this study, we comprehensively analyzed RNA sequencing (RNA-seq) data and clinical information using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We collected 10 m1A regulators and performed consensus clustering to determine m1A modification patterns in HCC. The CIBERSORT method was utilized to evaluate the level of immune cell infiltration. Principal component analysis was used to construct the m1A-score model. In the TCGA-LIHC cohort, the expression of all 10 m1A regulators was higher in tumor tissues than in normal control tissues, and 8 of 10 genes were closely related to the prognosis of HCC patients. Two distinct m1A methylation modification patterns (Clusters C1 and C2) were identified by the 10 regulators and were associated with different overall survival, TNM stage and tumor microenvironment (TME) characteristics. Based on the differentially expressed genes (DEGs) between C1 and C2, we identified three gene clusters (Clusters A, B and C). C1 with a better prognosis was mainly distributed in Cluster C, while Cluster A contained the fewest samples of C1. An m1A-score model was constructed using five m1A regulators related to prognosis. Patients with higher m1A scores showed a poorer prognosis than those with lower scores in the TCGA-LIHC and GSE14520 datasets. In conclusions, our study showed the vital role of m1A modification in the TME and progression of HCC. Quantitative evaluation of the m1A modification patterns of individual patients facilitates the development of more effective biomarkers for predicting the prognosis of patients with HCC.