The role of m6A RNA methylation in cancer metabolism

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 12, 2022

Abstract Metabolic reprogramming is one of the main characteristics malignant tumors, which due to flexible changes cell metabolism that can meet needs growth and maintain homeostasis tissue environments. Cancer cells obtain metabolic adaptation through a variety endogenous exogenous signaling pathways, not only promote cancer cells, but also start transformation process adapt tumor microenvironment. Studies show m6A RNA methylation widely involved in recombination cells. In eukaryotes, most abundant modification mRNA, almost all cycle stages, including regulation transcription, maturation, translation, degradation stability mRNA. M6A be physiological pathological processes, cancer. this review, we discuss role plays metabolism-related molecules aiming importance targeting regulating metabolism.

Language: Английский

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m6A modification: recent advances, anticancer targeted drug discovery and beyond

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 14, 2022

Abstract Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches modern discovery platforms used in an attempt to develop m6A-targeted drugs. Here, we provide update latest findings on critical roles cancer progression, summarize rational sources for agents from medicines computer-based chemosynthetic compounds. This review highlights potential targeting treatment proposes advantage artificial intelligence (AI) m6A-targeting Graphical abstract Three stages discovery: medicine-based natural products, chemical or synthesis, (AI)-assisted future.

Language: Английский

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m⁶A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer

Theranostics, Journal Year: 2020, Volume and Issue: 11(5), P. 2201 - 2217

Published: Dec. 16, 2020

Recent studies have highlighted the biological significance of RNA N6-methyladenosine (m6A) modification in tumorigenicity and progression. However, it remains unclear whether m6A modifications also potential roles immune regulation tumor microenvironment (TME) formation. Methods: In this study, we curated 23 regulators performed consensus molecular subtyping with NMF algorithm to determine patterns m6A-related gene signature colon cancer (CC). The ssGSEA CIBERSORT algorithms were employed quantify relative infiltration levels various cell subsets. An PCA based m6Sig scoring scheme was used evaluate individual tumors an response. Results: Three distinct identified among 1307 CC samples, which associated different clinical outcomes pathways. TME characterization revealed that highly consistent three known profiles: immune-inflamed, immune-excluded, immune-desert, respectively. Based on score, extracted from genes, patients can be divided into high low score subgroups. Patients lower characterized by prolonged survival time enhanced infiltration. Further analysis indicated correlated greater mutation loads, PD-L1 expression, higher rates SMGs (e.g., PIK3CA SMAD4). addition, scores showed a better responses durable benefits independent immunotherapy cohorts. Conclusions: This study highlights is significantly diversity complexity. Quantitatively evaluating will strengthen our understanding characteristics promote more effective strategies.

Language: Английский

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Insights into N6-methyladenosine and programmed cell death in cancer

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Jan. 28, 2022

Abstract N6-methyladenosine (m6A) methylation, the most common form of internal RNA modification in eukaryotes, has gained increasing attention and become a hot research topic recent years. M6A plays multifunctional roles normal abnormal biological processes, its role may vary greatly depending on position m6A motif. Programmed cell death (PCD) includes apoptosis, autophagy, pyroptosis, necroptosis ferroptosis, which involve breakdown plasma membrane. Based implications methylation PCD, regulators functional were comprehensively studied reported. In this review, we focus high-complexity links between different types PCD pathways, are then closely associated with initiation, progression resistance cancer. Herein, clarifying relationship is great significance to provide novel strategies for cancer treatment, potential prospect clinical application.

Language: Английский

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Role of m6A writers, erasers and readers in cancer

Experimental Hematology and Oncology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Aug. 9, 2022

Abstract The N(6)-methyladenosine (m6A) modification is the most pervasive of human RNAs. In recent years, an increasing number studies have suggested that m6A likely plays important roles in cancers. Many demonstrated involved biological functions cancer cells, such as proliferation, invasion, metastasis, and drug resistance. addition, closely related to prognosis patients. this review, we highlight advances understanding function various We emphasize importance progression look forward describe future research directions.

Language: Английский

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M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: May 6, 2022

Abstract Background Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially various cancers. However, oncogenic circRNAs hepatocellular carcinoma (HCC) is still largely unknown. Methods RNA sequencing was performed to identify significantly upregulated paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, xenograft mouse models were used investigate proliferation metastasis. Small interfering (siRNA) silence gene expression. immunoprecipitation, biotin pull-down, luciferase reporter assay western blot explore underlying molecular mechanisms. Results Hsa_circ_0095868 , derived from exon 5 MDK (named circMDK), identified as a new circRNA that HCC. The upregulation circMDK associated with modification N6-methyladenosine (m 6 A) poor survival patients. Mechanistically, sponged miR-346 miR-874-3p upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting activation PI3K/AKT/mTOR signaling pathway promote cell proliferation, migration invasion. Poly (β-amino esters) (PAEs) synthesized assist delivery siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects four liver including subcutaneous, metastatic, orthotopic patient-derived (PDX) models. Conclusions CircMDK could serve potential biomarker promotes via miR-346/874-3p-ATG16L1 axis. PAE-based improved stability efficiency targeting circMDK. PAE-siRNA nanoparticles metastasis vivo. Our current findings offer promising nanotherapeutic strategy for treatment Graphical

Language: Английский

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WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(6), P. 1137 - 1151

Published: Jan. 8, 2022

Language: Английский

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m⁶A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2‐mediated IGF1R mRNA stabilization

Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(6)

Published: June 1, 2021

Abstract Background Bone metastasis is the leading cause of tumor‐related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved progression multiple cancers. Nevertheless, role lncRNAs PCa bone remains largely unclear. Methods The expression cancer‐associated transcripts was analyzed published datasets and further verified clinical samples cell lines by RT‐qPCR situ hybridization assays. Colony formation assay, MTT cycle analysis, EdU Transwell migration invasion assays, wound healing vivo experiments were carried out investigate function transcript 6 ( PCAT6 ) tumor growth PCa. Bioinformatic RNA pull‐down, RIP assays conducted identify proteins binding potential targets . therapeutic targeting antisense oligonucleotides (ASO) explored Results upregulated tissues with increased predicted poor prognosis Functional found that knockdown significantly inhibited invasion, migration, proliferation vitro , as Mechanistically, METTL3 ‐mediated m A modification contributed upregulation an IGF2BP2 ‐dependent manner. Furthermore, IGF1R enhancing mRNA stability through / RNA‐protein three‐dimensional complex. Importantly, inhibition ASO showed against Finally, correlation demonstrated cells. Conclusions Our study uncovers a novel molecular mechanism which A‐induced axis promotes growth, suggesting may serve promising prognostic marker target bone‐metastatic

Language: Английский

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The role of RNA m⁵C modification in cancer metastasis

International Journal of Biological Sciences, Journal Year: 2021, Volume and Issue: 17(13), P. 3369 - 3380

Published: Jan. 1, 2021

Epigenetic modification plays a crucial regulatory role in the biological processes of eukaryotic cells.The recent characterization DNA and RNA methylation is still ongoing.Tumor metastasis has long been an unconquerable feature fight against cancer.As inevitable component epigenetic network, 5-methylcytosine associated with multifarious cellular systemic diseases, including cell migration cancer metastasis.Recently, gratifying progress achieved determining molecular interactions between m 5 C writers (DNMTs NSUNs), demethylases (TETs), readers (YTHDF2, ALYREF YBX1) RNAs.However, underlying mechanism mobility remains unclear.The functions are believed to regulate gene expression at post-transcription level involved metabolism movement.In this review, we emphatically summarize updates on components related networks.The content will be focused potential mechanisms diseases.We discuss relevant upstream downstream interacting molecules their associations metastasis.

Language: Английский

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Hakai is required for stabilization of core components of the m6A mRNA methylation machinery

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 18, 2021

Abstract N 6 -methyladenosine (m A) is the most abundant internal modification on mRNA which influences steps of metabolism and involved in several biological functions. The E3 ubiquitin ligase Hakai was previously found complex with components m A methylation machinery plants mammalian cells but its precise function remained to be investigated. Here we show that a conserved component methyltransferase Drosophila human cells. In , depletion results reduced levels altered A-dependent functions including sex determination. We ubiquitination domain required for dimerization interaction other members machinery, while catalytic activity dispensable. Finally, demonstrate loss destabilizes subunits complex, resulting impaired deposition. Our work adds functional molecular insights into mechanism writer complex.

Language: Английский

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