H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 461, P. 132582 - 132582

Published: Sept. 19, 2023

Language: Английский

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Chemically Modified Platforms for Better RNA Therapeutics

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 929 - 1033

Published: Jan. 29, 2024

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential disease prevention and treatment. However, despite their remarkable achievements, these encounter substantial challenges including low stability, susceptibility to degradation by nucleases, prominent negative charge, thereby hindering further development. Chemically modified platforms emerged as strategic innovation, focusing on precise alterations either RNA moieties or associated delivery vectors. This comprehensive review delves into platforms, underscoring significance augmenting performance translational prospects of therapeutics. It encompasses an in-depth analysis various chemically that been instrumental propelling therapeutics toward clinical utility. Moreover, scrutinizes rationale behind diverse chemical modification techniques aiming at optimizing therapeutic efficacy molecules, facilitating robust management. Recent empirical studies corroborating enhancement through modifications are highlighted. Conclusively, we offer profound insights transformative impact drugs delineates prospective trajectories for future development integration.

Language: Английский

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RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy

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

Published: March 27, 2024

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding pathophysiology, inspiring development therapeutics. As a crucial component epigenetics at post-transcription level, RNA modification significantly determines fates, further affecting various biological processes cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells different stages immunological contexts. In this review, we characterize distribution features, modifying mechanisms functions 8 modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively most studied types. Then regulatory roles these diverse health disease contexts comprehensively described, categorized as glucose, lipid, amino acid, mitochondrial metabolism. And highlight regulation modifications immunometabolism, influencing responses. Above all, provide thorough discussion about clinical implications metabolism-targeted therapy immunotherapy, progression modification-targeted agents, its potential RNA-targeted Eventually, give legitimate perspectives for future researches field from methodological requirements, mechanistic insights, to therapeutic applications.

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

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

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities

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

Published: May 22, 2024

Abstract Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance toxicity still remain. Due the advancement of immuno-oncology, an increasing number novel immunoregulatory targets mechanisms are being revealed, with relevant therapies promising improve clinical immunotherapy in foreseeable future. Therefore, comprehending larger picture is important. In this review, we analyze summarize current landscape preclinical translational mechanistic research, drug development, trials that brought about next-generation pharmacological anti-cancer agents candidates beyond classical immune checkpoint inhibitors. Along further clarification immunobiology advances antibody engineering, targeting additional inhibitory checkpoints, including LAG-3, TIM-3, TIGIT, CD47, B7 family members becoming important part research discovery, as structurally functionally optimized agonists co-stimulatory molecules T cells. Exemplified bispecific cell engagers, newly emerging bi-specific multi-specific antibodies can provide considerable benefits. Next-generation also include epigenetic drugs cytokine-based therapeutics. Cell therapies, vaccines, oncolytic viruses not covered review. This comprehensive review might aid development fastest possible adoption effective immuno-oncology modalities for benefit patients.

Language: Английский

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NSUN2 promotes colorectal cancer progression by enhancing SKIL mRNA stabilization

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(3)

Published: March 1, 2024

Abstract Background NOP2/Sun domain 2 (NSUN2) is one of the important RNA methyltransferases catalyzing 5‐methylcytosine (m5C) formation and participates in many critical bioprocesses. However, roles underlying molecular mechanisms NSUN2‐mediated m5C modification colorectal cancer (CRC) remain unclear. Methods To explore NSUN2 expression CRC, fresh tissue samples were collected Nsun2 knockout mouse was constructed. In vitro vivo functional assays conducted to assess role NSUN2. array bisulfite sequencing used investigate potential targets. The function on SKIL identified by m5C‐methylated‐RNA immunoprecipitation stability assays. Additionally, microarray analysis patient‐derived tumour xenograft (PDX) models define therapeutic Results highly expressed CRC correlated with poor patient survival. Moreover, silencing suppressed tumourigenesis progression models. studies suggested that promoted cell growth. Mechanistically, SKI‐like proto‐oncogene (SKIL) positively regulated NSUN2, NSUN2‐SKIL axis clinically relevant CRC. induced stabilized its mRNA, which mediated Y‐box binding protein 1 (YBX1). Elevated levels increased transcriptional coactivator PDZ‐binding motif (TAZ) activation. Conclusions Our findings highlight importance initiation via m5C‐YBX1‐dependent stabilization transcript, providing a promising targeted strategy for

Language: Английский

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Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: May 1, 2024

Abstract RNA modification, especially methylation, is a critical posttranscriptional process influencing cellular functions and disease progression, accounting for over 60% of all modifications. It plays significant role in metabolism, affecting processing, stability, translation, thereby modulating gene expression cell essential proliferation, survival, metastasis. Increasing studies have revealed the disruption metabolism mediated by methylation has been implicated various aspects cancer particularly metabolic reprogramming immunity. This profound implications tumor growth, metastasis, therapy response. Herein, we elucidate fundamental characteristics their impact on expression. We highlight intricate relationship between reprogramming, immunity, using well‐characterized phenomenon as framework to discuss methylation's specific roles mechanisms progression. Furthermore, explore potential targeting regulators novel approach therapy. By underscoring complex which contributes this review provides foundation developing new prognostic markers therapeutic strategies aimed at treatment.

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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Emerging role of RNA acetylation modification ac4C in diseases: Current advances and future challenges

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 213, P. 115628 - 115628

Published: May 27, 2023

Language: Английский

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Novel insight into RNA modifications in tumor immunity: Promising targets to prevent tumor immune escape

The Innovation, Journal Year: 2023, Volume and Issue: 4(4), P. 100452 - 100452

Published: May 29, 2023

•RNA modification is a novel hotspot of epigenetic research, affecting wide range physiological and pathological processes.•RNA plays an important role in tumor immunity.•RNA may be potential clinical therapeutic target to prevent immune escape. An immunosuppressive state typical feature the microenvironment. Despite dramatic success checkpoint inhibitor (ICI) therapy preventing cell escape from surveillance, primary acquired resistance have limited its use. Notably, recent trials shown that drugs can significantly improve outcome ICI various cancers, indicating importance modifications regulation tumors. Recently, RNA (N6-methyladenosine [m6A], N1-methyladenosine [m1A], 5-methylcytosine [m5C], etc.), areas been play crucial roles protumor antitumor immunity. In this review, we provide comprehensive understanding how m6A, m1A, m5C function immunity by directly regulating different cells as well indirectly through mechanisms, including modulating expression checkpoints, inducing metabolic reprogramming, secretion immune-related factors. Finally, discuss current status strategies targeting escape, highlighting their potential.

Language: Английский

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