The roles and implications of RNA m6A modification in cancer

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(8), P. 507 - 526

Published: May 23, 2023

Language: Английский

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The Proteins of mRNA Modification: Writers, Readers, and Erasers

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 145 - 173

Published: April 17, 2023

Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled large part by development tools for detecting RNA transcriptome wide, researchers uncovered a diverse epitranscriptome that serves an additional layer regulation beyond simple sequence. Here, we review proteins write, read, and erase these marks, with particular focus on most abundant internal modification, N6-methyladenosine (m6A). We first describe discovery key enzymes deposit remove m6A other discuss how our understanding has shaped views modification dynamics. then current models function reader knowledge evolved. Finally, highlight future directions field questions remain unanswered.

Language: Английский

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N6-methyladenosine-mediated gene regulation and therapeutic implications

Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 454 - 467

Published: April 15, 2023

Language: Английский

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Epigenetics-targeted drugs: current paradigms and future challenges

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Language: Английский

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tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 15, 2024

Abstract Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding (ncRNAs) produced by the specific cleavage precursor or mature tRNAs. tsRNAs involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting occurrence development human diseases, including cancers. Recent studies have shown that play an important role tumorigenesis regulating behaviors malignant proliferation, invasion metastasis, angiogenesis, immune response, tumor resistance, metabolism reprogramming. These may be potential targets for treatment. Furthermore, can exist abundantly stably bodily fluids (e.g., blood, serum, urine) form free encapsulated extracellular vesicles, intercellular communication microenvironment (TME). Meanwhile, their abnormal expression is closely related to clinicopathological features patients, staging, lymph node poor prognosis patients; thus, served novel liquid biopsy biomarker. This review summarizes discovery, production, analyzes molecular mechanisms applications therapy, which provide strategies early diagnosis targeted therapy tumors.

Language: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 4, 2024

Abstract Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older exhibit increased ferroptosis during HIRI. Inhibiting significantly attenuates HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated livers, especially Overexpressing FTO improves phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) transferrin receptor protein 1 (TFRC), two key positive contributors ferroptosis, targets. For ameliorative effect, requires the inhibition of Acsl4 Tfrc mRNA stability a m6A-dependent manner. Furthermore, nicotinamide mononucleotide can upregulate demethylase activity, suppressing decreasing Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway contributes pathogenesis HIRI, providing insight into clinical translation strategies related activity improve graft function after donor

Language: Английский

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Epigenetic Targets and Their Inhibitors in the Treatment of Idiopathic Pulmonary Fibrosis

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117463 - 117463

Published: March 1, 2025

Language: Английский

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Advances in targeting RNA modifications for anticancer therapy

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(7), P. 528 - 542

Published: May 4, 2023

Language: Английский

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2-Aminobenzothiazoles in anticancer drug design and discovery

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 135, P. 106477 - 106477

Published: March 20, 2023

Language: Английский

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