RNA modification: mechanisms and therapeutic targets

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Авг. 24, 2023

Abstract RNA modifications are dynamic and reversible chemical on substrate that regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes various diseases, such as development cancer other diseases. With help advanced sequencing technologies, role has caught increasing attention human diseases scientific research. In this review, we briefly summarized basic mechanisms several common modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing ac4C. Importantly, discussed their potential functions cancer, neurological disorders, cardiovascular metabolic genetic developmental well immune disorders. Through “writing-erasing-reading” mechanisms, regulate stability, translation, localization pivotal disease-related mRNAs to manipulate disease development. Moreover, also highlighted review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most which designed against m6A-related enzymes, METTL3, FTO ALKBH5. This provides clues for clinical therapy future study directions modification field. More in-depth studies further activators needed a thorough understanding epitranscriptomics diagnosis, treatment, prognosis

Язык: Английский

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

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Июнь 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.

Язык: Английский

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Research progress of N1-methyladenosine RNA modification in cancer

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Янв. 30, 2024

Abstract N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays pivotal role in the regulation of various biological functions and activities. Especially cancer cell invasion, proliferation cycle regulation. Over recent years, there has been burgeoning interest investigating m1A modification RNA. Most studies have focused on enrichment areas different regions. This review provides comprehensive overview methodologies employed for detection modification. Furthermore, this delves into key players modification, known as “writers,” “erasers,” “readers.” by methyltransferases, or writers, such TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed demethylases, erasers, including FTO ALKBH1, ALKBH3. It recognized m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, TYHDC1, also “readers”. Additionally, we explore intricate relationship between its regulators their implications development progression specific types cancer, discuss how can potentially facilitate discovery novel approaches diagnosis, treatment, prognosis. Our summary methylated adenosine methods regulatory mechanisms cancers useful insights

Язык: Английский

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

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 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.

Язык: Английский

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Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis

Biomedicines, Год журнала: 2023, Номер 11(7), С. 1852 - 1852

Опубликована: Июнь 28, 2023

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors HCC such as viral hepatitis (B, C), cirrhosis, tobacco alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), metabolic genetic diseases. Diagnosis is based on different methods imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance (MRI), diagnostic biomarkers. In this review, we examine epidemiology worldwide in Egypt well associated with development and, finally, provide updated biomarkers for diagnosis HCC, particularly early stages HCC. Several considered to diagnose including downregulated or upregulated protein markers secreted during development, circulating nucleic acids cells, metabolites, promising, recently identified quantitative proteomics through isobaric tags relative absolute quantitation (iTRAQ). addition, a model used improve sensitivity combined discussed.

Язык: Английский

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The functions and mechanisms of post-translational modification in protein regulators of RNA methylation: Current status and future perspectives

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 253, С. 126773 - 126773

Опубликована: Сен. 9, 2023

Язык: Английский

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Critical roles and clinical perspectives of RNA methylation in cancer

MedComm, Год журнала: 2024, Номер 5(5)

Опубликована: Май 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.

Язык: Английский

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PUS7‐dependent pseudouridylation of ALKBH3 mRNA inhibits gastric cancer progression

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(8)

Опубликована: Авг. 1, 2024

Abstract Background RNA pseudouridylation is a critical post‐transcriptional modification that influences gene expression and impacts various biological functions. Despite its significance, the role of mRNA in cancer remains poorly understood. This study investigates impact pseudouridine synthase 7 (PUS7)‐mediated Alpha‐ketoglutarate‐dependent Dioxygenase alkB Homolog 3 ( ALKBH3 ) gastric cancer. Methods Immunohistochemistry Western blotting were used to assess PUS7 protein levels human tissues. The relationship between progression was examined using 3D colony formation assays subcutaneous xenograft models. Real‐time quantitative PCR (RT‐qPCR), blotting, polysome profiling conducted investigate how regulates ALKBH3. A locus‐specific (Ψ) detection assay identify Ψ sites on mRNA. Results Our findings indicate significant reduction tissues compared adjacent non‐tumour Functional analyses reveal inhibits cell proliferation tumour growth via catalytic activity. Additionally, enhances translation efficiency by modifying U696 site with pseudouridine, thereby attenuating growth. Importantly, functions as suppressor cancer, closely correlated Conclusions PUS7‐dependent translation, suppressing progression. These highlight potential significance biology suggest therapeutic target for Highlights through activity mRNA, inhibiting tumourigenesis. are significantly tumours, which may be prognostic predictors targets patients

Язык: Английский

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m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling

International Journal of Oral Science, Год журнала: 2024, Номер 16(1)

Опубликована: Май 10, 2024

Abstract N 1 -methyladenosine (m A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 Pten conditional knockout (2cKO) mice, we found neoplastic transformation oral mucosa was accompanied by increased m A modification levels. Analysis A-associated genes identified TRMT61A as a key writer linked to cancer progression poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m promotes MYC protein synthesis, upregulating programmed death-ligand (PD-L1) expression. Moreover, levels were also elevated tumors treated with oncolytic herpes simplex virus (oHSV), contributing reactive PD-L1 upregulation. Therapeutic inhibition sustained oHSV-induced antitumor immunity reduced tumor growth, representing promising strategy alleviate resistance. These findings indicate that can prevent immune escape after oHSV therapy reducing expression, providing mutually reinforcing combination approach.

Язык: Английский

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N6-Methylandenosine-related lncRNAs as potential biomarkers for predicting prognosis and the immunotherapy response in pancreatic cancer

Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)

Опубликована: Янв. 21, 2025

Emerging evidence has shown that the N6-methyladenosine (m6A) modification of RNA plays key roles in tumorigenesis and progression various cancers. However, potential m6A long noncoding RNAs (lncRNAs) pancreatic cancer (PaCa) are still unknown. To analyze prognostic value m6A-related lncRNAs PaCa, an lncRNA signature was constructed as a risk model via Pearson's correlation univariate Cox regression analyses The Cancer Genome Atlas (TCGA) database. tumor microenvironment (TME), mutation burden, drug sensitivity PaCa were investigated by score analyses. We established consisting five lncRNAs, namely, LINC01091, AC096733.2, AC092171.5, AC015660.1, AC005332.6, which not only revealed significant differences immune cell infiltration associated with TME between high-risk low-risk groups but also predicted benefit immunotherapy for patients PaCa. Drugs such WZ8040, selumetinib, bortezomib identified more effective patients. Our results indicate could be independent indicator, may provide valuable insights identifying therapeutic approaches

Язык: Английский

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