The role of m6A modification in the biological functions and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Feb. 21, 2021

Abstract N 6 -methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher cells. m6A modified by methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, KIAA1429, and, removed demethylases, erasers, including FTO ALKBH5. It recognized m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 HNRNPA2B1, also known “readers”. Recent studies have shown that RNA plays essential role both physiological pathological conditions, initiation progression of different types human cancers. In this review, we discuss how methylation influences progressions hematopoietic, central nervous reproductive systems. We will mainly focus on recent progress identifying biological functions underlying molecular mechanisms methylation, its regulators downstream target genes, during cancer above propose process offer potential targets for therapy future.

Language: Английский

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m6A Modification in Coding and Non-coding RNAs: Roles and Therapeutic Implications in Cancer

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(3), P. 270 - 288

Published: March 1, 2020

Language: Английский

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Role of RNA modifications in cancer

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(6), P. 303 - 322

Published: April 16, 2020

Language: Английский

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m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: March 12, 2020

The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles RNA N6-methyladenosine (m6A) modification tumor microenvironment (TME) cell infiltration remain unknown.We comprehensively evaluated the m6A patterns 1938 gastric cancer samples based on 21 regulators, and systematically correlated these with TME cell-infiltrating characteristics. m6Ascore was constructed to quantify individual tumors using principal component analysis algorithms.Three distinct were determined. characteristics under three highly consistent phenotypes including immune-excluded, immune-inflamed immune-desert phenotypes. We evaluation within could predict stages inflammation, subtypes, stromal activity, genetic variation, patient prognosis. Low m6Ascore, characterized by increased mutation burden activation immunity, indicated an inflamed phenotype, 69.4% 5-year survival. Activation stroma lack effective observed high subtype, indicating a non-inflamed immune-exclusion poorer also linked neoantigen load enhanced anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients lower significant therapeutic advantages clinical benefits.This work revealed played nonnegligible role formation diversity complexity. Evaluating pattern will contribute enhancing our cognition characterization guiding more strategies.

Language: Английский

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A Unified Model for the Function of YTHDF Proteins in Regulating m6A-Modified mRNA

Cell, Journal Year: 2020, Volume and Issue: 181(7), P. 1582 - 1595.e18

Published: June 1, 2020

N6-methyladenosine (m6A) is the most abundant mRNA nucleotide modification and regulates critical aspects of cellular physiology differentiation. m6A thought to mediate its effects through a complex network interactions between different sites three functionally distinct cytoplasmic YTHDF m6A-binding proteins (DF1, DF2, DF3). In contrast prevailing model, we show that DF bind same m6A-modified mRNAs rather than mRNAs. Furthermore, find do not induce translation in HeLa cells. Instead, paralogs act redundantly degradation The ability regulate stability differentiation becomes evident only when all are depleted simultaneously. Our study reveals unified model function which subjected combined action proportion number sites.

Language: Английский

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The m6A reader YTHDF1 promotes ovarian cancer progression via augmenting EIF3C translation

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 48(7), P. 3816 - 3831

Published: Jan. 22, 2020

Abstract N 6-Methyladenosine (m6A) is the most abundant RNA modification in mammal mRNAs and increasing evidence suggests key roles of m6A human tumorigenesis. However, whether m6A, especially its ‘reader’ YTHDF1, targets a gene involving protein translation thus affects overall production cancer cells largely unexplored. Here, using multi-omics analysis for ovarian cancer, we identified novel mechanism EIF3C, subunit initiation factor EIF3, as direct target YTHDF1. YTHDF1 augments EIF3C an m6A-dependent manner by binding to m6A-modified mRNA concomitantly promotes translational output, thereby facilitating tumorigenesis metastasis cancer. frequently amplified up-regulation associated with adverse prognosis patients. Furthermore, but not abundance increased positively correlates expression patients, suggesting more relevant role Collectively, identify YTHDF1-EIF3C axis critical progression which can serve develop therapeutics treatment.

Language: Английский

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Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion

Cancer Cell, Journal Year: 2020, Volume and Issue: 38(1), P. 79 - 96.e11

Published: June 11, 2020

Language: Английский

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m ⁶ A RNA methylation: from mechanisms to therapeutic potential

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(3)

Published: Jan. 20, 2021

Language: Английский

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Targeting the epigenetic regulation of antitumour immunity

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(11), P. 776 - 800

Published: Sept. 14, 2020

Language: Английский

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The roles of DNA, RNA and histone methylation in ageing and cancer

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(10), P. 573 - 589

Published: July 3, 2019

Language: Английский

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