RNA modifications in cancer DOI Creative Commons

Han Wu,

Shi Chen, Xiang Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

The potential role of N7-methylguanosine (m7G) in cancer DOI Creative Commons

Yuejun Luo,

Yuxin Yao, Peng Wu

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 19, 2022

Abstract N 7 -methylguanosine (m7G), one of the most prevalent RNA modifications, has recently attracted significant attention. The m7G modification actively participates in biological and pathological functions by affecting metabolism various molecules, including messenger RNA, ribosomal microRNA, transfer RNA. Increasing evidence indicates a critical role for human disease development, especially cancer, aberrant levels are closely associated with tumorigenesis progression via regulation expression multiple oncogenes tumor suppressor genes. Currently, underlying molecular mechanisms cancer not comprehensively understood. Here, we review current knowledge regarding potential function modifications discuss future m7G-related diagnostic therapeutic strategies.

Language: Английский

Citations

170
Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets DOI Creative Commons

Jing Yang,

Jin Xu, Wei Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 22, 2023

Abstract Over decades, researchers have focused on the epigenetic control of DNA-templated processes. Histone modification, DNA methylation, chromatin remodeling, RNA and noncoding RNAs modulate many biological processes that are crucial to development cancers. Dysregulation epigenome drives aberrant transcriptional programs. A growing body evidence suggests mechanisms modification dysregulated in human cancers might be excellent targets for tumor treatment. Epigenetics has also been shown influence immunogenicity immune cells involved antitumor responses. Thus, application therapy cancer immunotherapy their combinations may important implications Here, we present an up-to-date thorough description how modifications cell responses microenvironment (TME) epigenetics internally modify TME. Additionally, highlight therapeutic potential targeting regulators immunotherapy. Harnessing complex interplay between immunology develop therapeutics combine thereof is challenging but could yield significant benefits. The purpose this review assist understanding impact TME, so better immunotherapies can developed.

Language: Английский

Citations

143
Aberrant translation regulated by METTL1/WDR4‐mediated tRNA N7‐methylguanosine modification drives head and neck squamous cell carcinoma progression DOI
Jie Chen, Kang Li, Jianwen Chen

et al.

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(3), P. 223 - 244

Published: Feb. 18, 2022

Cancer cells selectively promote the translation of oncogenic transcripts to stimulate cancer progression. Although growing evidence has revealed that tRNA modifications and related genes participate in this process, their roles head neck squamous cell carcinoma (HNSCC) remain largely uncharacterized. Here, we sought investigate function mechanisms transfer RNA (tRNA) N7-methylguanosine (m7 G) modification regulating occurrence development HNSCC.Cell lost-of-function gain-of-function assays, xenograft models, conditional knockout knockin mouse models were used study physiological functions m7 G HNSCC tumorigenesis. expression profiling, mRNA profiling rescue assays performed uncover underlying molecular mechanisms. Single-cell sequencing (scRNA-seq) was conducted explore tumor microenvironment changes.The methyltransferase complex components Methyltransferase-like 1 (METTL1)/WD repeat domain 4 (WDR4) upregulated associated with a poor prognosis. Functionally, METTL1/WDR4 promoted progression metastasis cell-based transgenic models. Mechanistically, ablation METTL1 reduced levels 16 tRNAs, inhibiting subset transcripts, including phosphatidylinositol-3-kinase/protein kinase B/mammalian target rapamycin (PI3K/AKT/mTOR) signaling pathway. In addition, chemical modulators PI3K/Akt/mTOR pathway reversed effects Mettl1 HNSCC. Furthermore, scRNA-seq results altered immune landscape cell-cell interaction between stromal compartment.The found malignancy through global translation, PI3K/AKT/mTOR pathway, alter landscape. could be promising treatment for patients.

Language: Английский

Citations

134
N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis DOI Creative Commons
Hui Han, Chunlong Yang, Jieyi Ma

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 18, 2022

Abstract Mis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while molecular mechanisms remain unclear. Here we reveal that tRNA m 7 G methyltransferase complex proteins METTL1 WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues associated with poor ESCC prognosis. In addition, progression via activity vitro vivo. Mechanistically, or knockdown leads decreased expression G-modified tRNAs reduces a subset transcripts enriched RPTOR/ULK1/autophagy pathway. Furthermore, models using Mettl1 conditional knockout knockin mice uncover essential function promoting tumorigenesis Our study demonstrates important mis-regulated modification ESCC, suggest targeting its downstream signaling axis could be promising therapeutic target for treatment.

Language: Английский

Citations

125
Structures and mechanisms of tRNA methylation by METTL1–WDR4 DOI
Victor M. Ruiz-Arroyo, Rishi Raj, Kesavan Babu

et al.

Nature, Journal Year: 2023, Volume and Issue: 613(7943), P. 383 - 390

Published: Jan. 4, 2023

Language: Английский

Citations

68
RNA modification: mechanisms and therapeutic targets DOI Creative Commons
Lei Qiu, Jing Qian, Yanbo Li

et al.

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 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

Language: Английский

Citations

68
RNA modifications in cancer DOI

Qiling Tang,

Lvyuan Li,

Yumin Wang

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(2), P. 204 - 221

Published: April 24, 2023

Language: Английский

Citations

66
Structural basis of regulated m7G tRNA modification by METTL1–WDR4 DOI
Jiazhi Li, Longfei Wang, Quentin Hahn

et al.

Nature, Journal Year: 2023, Volume and Issue: 613(7943), P. 391 - 397

Published: Jan. 4, 2023

Language: Английский

Citations

63
Methyltransferase-like proteins in cancer biology and potential therapeutic targeting DOI Creative Commons

Yanan Qi,

Zhu Liu,

Lian‐Lian Hong

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 2, 2023

Abstract RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family proteins plays critical role in modification, methylating various types RNAs, including mRNA, tRNA, microRNA, rRNA, mitochondrial RNAs. METTL consist unique seven-beta-strand domain, which binds to methyl donor SAM catalyze transfer. The most typical member METTL3/METTL14 forms methyltransferase complex involved N 6-methyladenosine (m6A) RNA, regulating tumor proliferation, metastasis invasion, immunotherapy resistance, metabolic reprogramming cells. METTL1, METTL4, METTL5, METTL16 have also been identified some regulatory ability tumorigenesis, rest members rely on their activity for methylation different nucleotides, proteins, small molecules, regulate translation affect processes such as cell differentiation development. Herein, we summarize literature METTLs last three years elucidate roles human cancers provide theoretical basis future use potential therapeutic targets.

Language: Английский

Citations

59
Writers, readers, and erasers RNA modifications and drug resistance in cancer DOI Creative Commons
Di Chen, Xinyu Gu,

Yeltai Nurzat

et al.

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

Citations

18