The Emerging Role of N6-Methyladenosine RNA Methylation as Regulators in Cancer Therapy and Drug Resistance

Chen, Zhaolin; Hu, Ying; Jin, Le; Yang, Fan; Ding, Haiwen; Zhang, Lei; Li, Lili; Pan, Tingting

doi:10.3389/fphar.2022.873030

Cited by 13 publications

(12 citation statements)

References 186 publications

(190 reference statements)

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“…These epitransciptomic changes were shown to promote EBV infection in vitro [38,39]. Furthermore, accumulating evidence demonstrated that abnormal changes in the m 6 A levels are associated with human tumorigenesis and drug resistance [40][41][42].…”

Section: Global Dna Methylation Levels Allow the Discrimination Betwe...mentioning

confidence: 98%

Global DNA Methylation Levels in Epstein-Barr-Virus-Positive Iraqi Patients with Acute Lymphoblastic Leukaemia

Lafta

Al-Jumaily²,

Rasoul³

2023

Iraqi Journal of Science

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Acute lymphoblastic leukemia (ALL) is one of the commonest hematological malignancies affecting children and adults. Recent evidence suggests an involvement of Epstein-Barr virus (EBV) in ALL pathogenicity. Epigenetic aberration, especially altered DNA methylation marks, is a key event of cancer development. The present study aims to investigate how the ALL epimethylome reacts to viral infection through the assessment of the total 5-methylcytosine (5mC) levels in ALL patients, according to EBV infection. The 5mC global DNA methylation levels in 50 diagnosed ALL patients (age mean 26.23 yrs; age range 10-60 yrs) and 25 age-matched healthy controls were assessed using MethylFlash™ Methylated DNA Quantification Kit. Acute primary EBV infection in the studied subjects was detected by measuring Epstein-Barr Virus (EBNA-1) IgG levels using ELISA. The results showed a significant (P˂0.001) decrease in 5mC levels in ALL-EBV positive cases as compared to those who were negative for EBV infection (0.234±0.117 vs. 0.441±0.153, respectively). The reduction in the average 5mC level seemed to be negatively correlated with EBV viral load (r = -0.599, p= 0.001). Additionally, 5mC levels were able to distinguish between ALL main subtypes (B-ALL and T-ALL; derived from B or T lymphocytes), where T-ALL cases showed significantly (P=0.005) higher 5mC levels than those of B-ALL cases (0.587±0.070 vs. 0.180±0.092, respectively). Also significantly (P=0.04) lower 5mC levels were detected in Philadelphia chromosome-positive (Ph+) ALL cases than in those who were negative to this genetic abnormality (Ph- -ALL) (0.13±0.021 vs. 0.179±0.093, respectively). Overall, the findings of the present study suggest an involvement of EBV infection in ALL pathogenicity, with the potential of utilizing the differences in global DNA methylation levels in ALL patients' risk stratification.

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Section: Global Dna Methylation Levels Allow the Discrimination Betwe...mentioning

confidence: 98%

Global DNA Methylation Levels in Epstein-Barr-Virus-Positive Iraqi Patients with Acute Lymphoblastic Leukaemia

Lafta

Al-Jumaily²,

Rasoul³

2023

Iraqi Journal of Science

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“…Abnormal RNA modifications have been detected in a variety of diseases [ 24 , 33 , 34 ]. In particular, studies showed that RNA modification dysregulations could play important roles in cancer initiation, metastasis, prognosis, and responses to therapies [ 23 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Mechanistically, RNA modifications could affect the expression of genes involved in important oncogenic pathways such as the Wnt/β-catenin pathway, the PI3K-Akt-mTOR pathway, the JAK-STAT pathway, the MAPK pathway, the p53 pathway, the Hippo Pathway, etc.…”

Section: Epitranscriptomicsmentioning

confidence: 99%

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

Yang

Wang

2022

IJMS

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Metals are common toxic environmental pollutants. Acute or chronic exposure to metal pollutants causes severe adverse health effects in animals and humans, such as developmental retardation, abnormal metabolism, and disorders of cardiovascular, neurologic, respiratory, reproductive, and urologic systems. Moreover, several metals (arsenic, cadmium, chromium, and nickel) are classified as potent Group I carcinogens and cause various types of cancer in humans. Although the toxicity and carcinogenicity of metal pollutants are well recognized, the underlying mechanisms have not been clearly defined. The epitranscriptome includes all kinds of chemical modifications of all forms of RNA molecules inside a cell. Recent progresses in demonstrating the reversible pattern of RNA modifications and their roles in physiology and pathogenesis represent a breakthrough in the field of RNA biology and function study. The epitranscriptomic study is now an exciting emerging field in toxicology research. While few studies have been conducted so far to determine the epitranscriptomic effects of metal pollutants, they offer novel insights for understanding the mechanisms of metal toxicity and carcinogenesis. The goal of this review is to discuss recent studies on the epitranscriptomic effects of metals and propose some thoughts for future studies in the field.

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“…Base modifications in mRNA, such as adenosine to inosine deamination (A-to-I editing), N6-methyladenosine (m 6 A) modification and cytosine to uracil deamination, play pivotal roles in various types of biological and pathological processes [ 1 ]. A-to-I editing and m 6 A modification are two of the most common RNA modifications controlling gene expression in mammals, and they have emerged as hot topics in cancer research [ 2 , 3 ]. A-to-I RNA editing is carried out by the adenosine deaminases acting on RNAs (ADARs: ADAR1/2) through conversion of adenosine to inosine within cellular RNA in mammals [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

RNA Editing Enzyme ADAR1 Regulates METTL3 in an Editing Dependent Manner to Promote Breast Cancer Progression via METTL3/ARHGAP5/YTHDF1 Axis

Wang

Yin

et al. 2022

IJMS

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A-to-I RNA editing and m6A modification are two of the most prevalent types of RNA modifications controlling gene expression in mammals and play very important roles in tumorigenesis and tumor progression. However, the functional roles and correlations of these two RNA modifications remain to be further investigated in cancer. Herein, we show that ADAR1, an A-to-I RNA-editing enzyme, interacts with METTL3 and increases its protein level to promote the proliferation, migration and invasion of breast cancer cells through a mechanism connecting ADAR1, METTL3 and YTHDF1. We show that both ADAR1 and METTL3 are upregulated in breast cancer samples, and ADAR1 positively correlates with METTL3; ADAR1 edits METTL3 mRNA and changes its binding site to miR532-5p, leading to increased METTL3 protein, which further targets ARHGAP5, recognized by YTHDF1. Additionally, we show that loss of ADAR1 significantly inhibits breast cancer growth in vivo. Collectively, our findings identify the ADAR1–METTL3 axis as a novel, important pathway that connects A-to-I editing and m6A RNA modifications during breast cancer progression.

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The Emerging Role of N6-Methyladenosine RNA Methylation as Regulators in Cancer Therapy and Drug Resistance

Cited by 13 publications

References 186 publications

Global DNA Methylation Levels in Epstein-Barr-Virus-Positive Iraqi Patients with Acute Lymphoblastic Leukaemia

Global DNA Methylation Levels in Epstein-Barr-Virus-Positive Iraqi Patients with Acute Lymphoblastic Leukaemia

The Epitranscriptomic Mechanism of Metal Toxicity and Carcinogenesis

RNA Editing Enzyme ADAR1 Regulates METTL3 in an Editing Dependent Manner to Promote Breast Cancer Progression via METTL3/ARHGAP5/YTHDF1 Axis

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