Abstract:These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m A modification in tumor progression. (Hepatology 2017;65:529-543).
“…These studies suggest that RNA demethylases are a potential target for anti-glioblastoma therapy [69], [70]. In hepatocellular carcinoma (HCC), downregulation of METTL14 results in lower m 6 A levels, and enhances the metastatic capacity of HCC cells [71]. The processing of the metastasis-associated miRNA miR126 requires METTL14 activity and is involved in HCC metastasis [71] (Figure 2B).Figure 2 Links between m 6 A regulation and cancer Schematic representation of m 6 A pathway components and targets involved in cancer progression.…”
Section: M6a and Cancermentioning
confidence: 99%
“…In hepatocellular carcinoma (HCC), downregulation of METTL14 results in lower m 6 A levels, and enhances the metastatic capacity of HCC cells [71]. The processing of the metastasis-associated miRNA miR126 requires METTL14 activity and is involved in HCC metastasis [71] (Figure 2B).Figure 2 Links between m 6 A regulation and cancer Schematic representation of m 6 A pathway components and targets involved in cancer progression. Blue lines represent methylation, red lines represent demethylation and green lines indicate m 6 A reader proteins.…”
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.
“…These studies suggest that RNA demethylases are a potential target for anti-glioblastoma therapy [69], [70]. In hepatocellular carcinoma (HCC), downregulation of METTL14 results in lower m 6 A levels, and enhances the metastatic capacity of HCC cells [71]. The processing of the metastasis-associated miRNA miR126 requires METTL14 activity and is involved in HCC metastasis [71] (Figure 2B).Figure 2 Links between m 6 A regulation and cancer Schematic representation of m 6 A pathway components and targets involved in cancer progression.…”
Section: M6a and Cancermentioning
confidence: 99%
“…In hepatocellular carcinoma (HCC), downregulation of METTL14 results in lower m 6 A levels, and enhances the metastatic capacity of HCC cells [71]. The processing of the metastasis-associated miRNA miR126 requires METTL14 activity and is involved in HCC metastasis [71] (Figure 2B).Figure 2 Links between m 6 A regulation and cancer Schematic representation of m 6 A pathway components and targets involved in cancer progression. Blue lines represent methylation, red lines represent demethylation and green lines indicate m 6 A reader proteins.…”
Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.
“…The clinical data also revealed that patients with decreased METTL14 showed worse recurrence‐free survival and overall survival 50. METTL14 deficiency enhanced the metastatic capacity of HCC cells, and conversely, overexpression of METTL14 suppressed cell migration and invasion 50. Further experiments demonstrated that pri‐miR‐126 was a direct target of METTL14 with m 6 A modification and m 6 A‐modified pri‐miR‐126 bound to DGCR8 to induce the expression of mature miR‐126 consequently.…”
Section: The Dual Role Of M6a Modification In Human Cancersmentioning
confidence: 99%
“…For hepatocellular carcinoma (HCC), the METTL14 expression and m 6 A level exhibited a converse tendency with the development of HCC, particularly in metastatic HCC. The clinical data also revealed that patients with decreased METTL14 showed worse recurrence‐free survival and overall survival 50. METTL14 deficiency enhanced the metastatic capacity of HCC cells, and conversely, overexpression of METTL14 suppressed cell migration and invasion 50.…”
Section: The Dual Role Of M6a Modification In Human Cancersmentioning
As the most abundant and reversible RNA modification in eukaryotic cells, m6A triggers a new layer of epi‐transcription. M6A modification occurs through a methylation process modified by “writers” complexes, reversed by “erasers”, and exerts its role depending on various “readers”. Emerging evidence shows that there is a strong association between m6A and human diseases, especially cancers. Herein, we review bi‐aspects of m6A in regulating cancers mediated by the m6A‐associated proteins, which exert vital and specific roles in the development of various cancers. Generally, the m6A modification performs promotion or inhibition functions (dual role) in tumorigenesis and progression of various cancers, which suggests a new concept in cancer regulations. In addition, m6A‐targeted therapies including competitive antagonists of m6A‐associated proteins may provide a new tumour intervention in the future.
“…and Ma et al. demonstrated that m 6 A modification is associated with the progression and metastasis of hepatocellular carcinoma . Drug‐induced hepatotoxicity is a major challenge faced by clinicians and seriously endangers human health.…”
Ribonucleic acid N6‐methyladenosine methylation plays an important role in a variety of biological processes and diseases. Acetaminophen‐induced hepatotoxicity is one of the major challenges faced by clinicians. To date, the link between N6‐methyladenosine and acetaminophen‐induced hepatotoxicity has not been studied. In this study, a simple ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the simultaneous determination of five nucleosides (adenosine, uridine, cytidine, guanosine, and N6‐methyladenosine) in messenger ribonucleic acid. After enzymatic digestion of messenger ribonucleic acid, the nucleosides sample was separated on an Acquity UPLC column with gradient elution using methanol and 0.02% formic acid water, and detected by a Qtrap 4500 mass spectrometer with an electrospray ionization mode. The method was validated over the concentration ranges of 4–800 ng/mL for adenosine, uridine, cytidine, and guanosine and 0.1–20 ng/mL for N6‐methyladenosine. It was successfully applied to the determination of N6‐methyladenosine levels in liver messenger ribonucleic acid in an acetaminophen‐induced hepatotoxicity mouse model and a control group. This study offers a method for the determination of nucleoside contents in epigenetic studies and constitutes the first step toward the investigation of ribonucleic acid methylation in acetaminophen‐induced hepatotoxicity, which will facilitate the elucidation of its mechanism.
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