Helicobacter pylori reduces METTL14-mediated VAMP3 m6A modification and promotes the development of gastric cancer by regulating LC3C-mediated c-Met recycling DOI Creative Commons

Xixi Cui,

Mingjie Chang,

Yuqiong Wang

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 18, 2025

Helicobacter pylori (H. pylori) plays an important role in the malignant transformation of gastric mucosa from chronic inflammation to cancer. However, mechanisms underlying epigenetic regulation carcinogenesis mediated by H. remain unclear. Here, we uncover that inhibits METTL14 upregulating ATF3. cancer (GC) cell proliferation and metastasis vitro vivo. Downregulation Vesicle-associated membrane protein-3 (VAMP3) reducing m6A modification level VAMP3 mRNA stability IGF2BP2-dependent mRNA. also accelerates progression GC regulating VAMP3/LC3C-mediated c-Met recycling. Moreover, expression Hp+ gastritis tissues is much lower than Hp- tissues. levels are downregulated notably cancerous patients with GC. Therefore, our results show a novel METTL14-VAMP3-LC3C-c-Met signalling axis development infection, which reveals mechanism for provides potential prognostic biomarkers progression.

Language: Английский

Methionine deficiency facilitates antitumour immunity by altering m6A methylation of immune checkpoint transcripts DOI Creative Commons
Ting Li,

Yue‐Tao Tan,

Yan‐Xing Chen

et al.

Gut, Journal Year: 2022, Volume and Issue: 72(3), P. 501 - 511

Published: July 8, 2022

Objective Methionine metabolism is involved in a myriad of cellular functions, including methylation reactions and redox maintenance. Nevertheless, it remains unclear whether methionine metabolism, RNA antitumour immunity are molecularly intertwined. Design The effect methionine-restricted diet (MRD) feeding was assessed murine models. mechanisms YTH domain-containing family protein 1 (YTHDF1) tumour immune escape were determined vitro vivo. synergistic effects MRD or YTHDF1 depletion with PD-1 blockade also investigated. Results We found that dietary restriction reduced growth enhanced by increasing the number cytotoxicity tumour-infiltrating CD8 + T cells different mouse Mechanistically, S-adenosylmethionine derived from promoted N 6 -methyladenosine (m A) translation checkpoints, PD-L1 V-domain Ig suppressor cell activation (VISTA), cells. Furthermore, m A-specific binding inhibited restoring infiltration cells, synergised for better control. Clinically, expression correlated poor prognosis immunotherapy outcomes cancer patients. Conclusions play critical role anticancer through regulating functions Targeting could be potential new strategy immunotherapy.

Language: Английский

Citations

117
C1q+ macrophages: passengers or drivers of cancer progression DOI Creative Commons

Margot Revel,

Catherine Sautès‐Fridman, Wolf H. Fridman

et al.

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(7), P. 517 - 526

Published: March 12, 2022

Language: Английский

Citations

103
METTL16 promotes hepatocellular carcinoma progression through downregulating RAB11B-AS1 in an m6A-dependent manner DOI Creative Commons

Yun-zhang Dai,

Yong-da Liu, Jie Li

et al.

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: May 20, 2022

The molecular mechanisms driving hepatocellular carcinoma (HCC) remain largely unclear. As one of the major epitranscriptomic modifications, N6-methyladenosine (m6A) plays key roles in HCC. aim this study was to investigate expression, roles, and action RNA methyltransferase methyltransferase-like protein 16 (METTL16) HCC.The expression METTL16 RAB11B-AS1 determined by RT-qPCR. regulation investigated immunoprecipitation (RIP), methylated RIP (MeRIP), stability assays. In vitro vivo gain- loss-of-function assays were performed RAB11B-AS1.METTL16 upregulated HCC, its increased correlated with poor prognosis HCC patients. promoted cellular proliferation, migration, invasion, repressed apoptosis, tumoral growth vivo. directly bound long noncoding (lncRNA) RAB11B-AS1, induced m6A modification decreased transcript, leading downregulation RAB11B-AS1. Conversely METTL16, is downregulated patients Furthermore, negatively tissues. inhibited Functional rescue revealed that overexpression reversed oncogenic HCC.This identified METTL16/RAB11B-AS1 regulatory axis which represented novel targets for treatment.

Language: Английский

Citations

91
Functions, mechanisms, and therapeutic implications of METTL14 in human cancer DOI Creative Commons

Qian Guan,

Huiran Lin,

Lei Miao

et al.

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

Published: Feb. 3, 2022

Abstract RNA modification plays a crucial role in many biological functions, and its abnormal regulation is associated with the progression of cancer. Among them, N 6 -methyladenine (m A) most abundant modification. Methyltransferase-like 14 (METTL14) central component m A methylated transferase complex, which involved dynamic reversible process METTL14 acts as both an oncogene tumor suppressor gene to regulate occurrence development various cancers. The level induced by related tumorigenesis, proliferation, metastasis, invasion. To date, molecular mechanism malignant tumors has not been fully studied. In this paper, we systematically summarize latest research progress on new biomarker for cancer diagnosis function human discuss potential clinical application. This study aims provide ideas targeted therapy improved prognoses

Language: Английский

Citations

81
N6-methyladenosine-mediated gene regulation and therapeutic implications DOI
Yujiao Liu, Dan Yang, Tao Liu

et al.

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

Published: April 15, 2023

Language: Английский

Citations

62
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
The promising role of tumor-associated macrophages in the treatment of cancer DOI
Hongbin Wang, Xueying Wang, Xin Zhang

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 73, P. 101041 - 101041

Published: Jan. 3, 2024

Language: Английский

Citations

58
m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion DOI Creative Commons
Xiaoxue Cao,

Qishun Geng,

Danping Fan

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

Citations

56
Methylation across the central dogma in health and diseases: new therapeutic strategies DOI Creative Commons
Ruochen Liu, Erhu Zhao,

Huijuan Yu

et al.

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

Published: Aug. 24, 2023

The proper transfer of genetic information from DNA to RNA protein is essential for cell-fate control, development, and health. Methylation DNA, RNAs, histones, non-histone proteins a reversible post-synthesis modification that finetunes gene expression function in diverse physiological processes. Aberrant methylation caused by mutations or environmental stimuli promotes various diseases accelerates aging, necessitating the development therapies correct disease-driver imbalance. In this Review, we summarize operating system across central dogma, which includes writers, erasers, readers, reader-independent outputs. We then discuss how dysregulation contributes neurological disorders, cancer, aging. Current small-molecule compounds target modifiers show modest success certain cancers. methylome-wide action lack specificity lead undesirable biological effects cytotoxicity, limiting their therapeutic application, especially with monogenic cause different directions changes. Emerging tools capable site-specific manipulation hold great promise solve dilemma. With refinement delivery vehicles, these new are well positioned advance basic research clinical translation field.

Language: Английский

Citations

56
RNA Modification in the Immune System DOI Creative Commons
Dali Han,

Meng Xu

Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 41(1), P. 73 - 98

Published: April 26, 2023

Characterization of RNA modifications has identified their distribution features and molecular functions. Dynamic changes in modification on various forms are essential for the development function immune system. In this review, we discuss value innovative profiling technologies to uncover these diverse, dynamic cells within healthy diseased contexts. Further, explore our current understanding mechanisms whereby aberrant modulate milieu tumor microenvironment point out outstanding research questions.

Language: Английский

Citations

45