New insights into N6-methyladenosine in hepatocellular carcinoma immunotherapy DOI Creative Commons

Mengran Li,

Hu Tian, Yanshuang Zhuang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

N6-methylation is a modification in which methyl group added to the adenine base of nucleotide. This crucial for controlling important functions that are vital gene expression, including mRNA splicing, stability, and translation. Due its intricate participation both normal cellular processes course disease, as well critical role determining cell fate, N6-methyladenosine (m 6 A) alteration has recently attracted lot interest. The formation progression many diseases, especially cancer, can be attributed dysregulated m A alteration, cause disturbances variety functions, such immunological responses, proliferation, differentiation. In this study, we examine how dysregulation affects hepatocellular carcinoma (HCC), with particular emphasis on it contributes evasion carcinogenesis. We also investigate potential novel therapeutic target, providing new perspectives approaches meant enhance clinical results patients HCC.

Language: Английский

Salsolinol as an RNA m6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy DOI Creative Commons

Jianan Wang,

Yuanyuan Ran, Zihan Li

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(3), P. 887 - 899

Published: May 17, 2024

JOURNAL/nrgr/04.03/01300535-202503000-00032/figure1/v/2025-03-16T133445Z/r/image-tiff Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Sal) is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an environmental toxin Parkinson’s disease. However, the mechanism by which Sal mediates dopaminergic neuronal death remains unclear. In this study, we found significantly enhanced global level of N 6 -methyladenosine (m A) RNA methylation in PC12 cells, mainly inducing downregulation expression m A demethylases fat mass obesity-associated protein (FTO) alkB homolog 5 (ALKBH5). sequencing analysis showed downregulated Hippo signaling pathway. The reader YTH domain-containing family 2 (YTHDF2) promoted degradation A-containing Yes-associated 1 ( YAP1 ) mRNA, downstream key effector Additionally, autophagy, indicating mutual regulation between autophagy can lead to neurotoxicity. These findings reveal role on suggest may act as inducer mediating through autophagy. Our results provide greater insights into neurotoxic effects isoquinolines compared other studies be reference for assessing involvement pathogenesis

Language: Английский

Citations

4
METTL14-Mediated m6A Modification of TUG1 Represses Ferroptosis in Alzheimer's Disease via Inhibiting GDF15 Ubiquitination DOI Creative Commons

Xunhu Gu,

Yuanqing Song,

Xu Liu

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(8)

Published: Aug. 21, 2024

Background: Alzheimer’s disease (AD) is a neurodegenerative that remains serious global health issue. Ferroptosis has been recognized as vital driver of pathological progression AD. However, the detailed regulatory mechanisms ferroptosis during AD remain unclear. This study aimed to explore role and mechanism methyltransferase like 14 (METTL14) in models. Methods: Serum samples were collected from 18 patients healthy volunteers evaluate clinical correlation. Scopolamine-treated mice Aβ1–42-stimulated SH-SY5Y cells served vivo vitro models was detected by reactive oxygen species (ROS), Fe2+, total iron levels, ferroptosis-related proteins glutathione peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11). Cell viability analyzed 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The N6-methyladenosine (m6A) modification RNA methylation quantification kit methylated immunoprecipitation sequencing-quantitative real-time polymerase chain reaction (MeRIP-qPCR). Molecular investigated pull-down, (RIP), co-immunoprecipitation (Co-IP) assays. Cognitive disorder measured Morris water maze test. Results: METTL14 down-regulated, while lncRNA taurine upregulated gene 1 (TUG1) up-regulated experimental Functional experiments demonstrated overexpression or TUG1 silencing effectively attenuated Aβ1–42-induced neurotoxicity cells. Mechanistically, METTL14-mediated m6A reduced stability TUG1. Moreover, promoted ubiquitination degradation growth differentiation factor 15 (GDF15) directly interacted with Smad ubiquitin (SMURF1), which consequently inactivated nuclear erythroid 2-related 2 (NRF2). Rescue indicated GDF15 depletion reversed sh-TUG1-mediated protection against neurotoxicity. Finally, Mettl14 repressed ameliorate cognitive via modulating Tug1/Gdf15/Nrf2 pathway vivo. Conclusion: inhibited development activate GDF15/NRF2 axis, providing novel therapeutic target for

Language: Английский

Citations

4
RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system DOI Creative Commons
Lu Liu, Yujia Zhao, Feng Zhang

et al.

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Neurodegenerative diseases (NDs) constitute a significant public health challenge, as they are increasingly contributing to global mortality and morbidity, particularly among the elderly population. Pathogenesis of NDs is intricate multifactorial. Recently, post-transcriptional modifications (PTMs) RNA, with particular focus on mRNA methylation, have been gaining increasing attention. At present, several regulatory genes associated methylation identified closely neurodegenerative disorders. This review aimed summarize RNA enzymes system, including writer, reader, eraser proteins delve into their functions in central nervous system (CNS), hoping open new avenues for exploring mechanisms therapeutic strategies NDs. studies highlighted critical role development function CNS, abnormalities this process may contribute brain damage NDs, aberrant expression involved has implicated onset

Language: Английский

Citations

0
N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1 DOI

Renjie Xiao,

Tianjiao Wang, Depei Wu

et al.

World Journal of Diabetes, Journal Year: 2025, Volume and Issue: 16(3)

Published: Jan. 20, 2025

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes. N6-methyladenosine (m6A)-related epigenetic regulation widely involved the pathogenesis of diabetes complications. However, function m6A methyltransferase Wilms tumor 1-associated protein (WTAP) diabetic healing remains elusive. AIM To investigate potential regulatory mechanism WTAP during healing. METHODS Human umbilical vein endothelial cells (HUVECs) were induced high glucose (HG) to establish vitro cell model. Male BALB/c mice intraperitoneally injected streptozotocin mimic diabetes, full-thickness excision was made HG-induced HUVECs mouse models treated siRNAs DNA 1 (DNMT1) overexpression vectors. Cell viability migration ability detected by counting kit-8 Transwell assays. In angiogenesis measured using tube formation experiment. The images wounds captured, re-epithelialization collagen deposition skin tissues analyzed hematoxylin eosin staining Masson’s trichrome staining. RESULTS expression several methyltransferases, including METTL3, METTL14, METTL16, KIAA1429, WTAP, RBM15, measured. exhibited most elevation compared normal control. depletion notably restored enhanced suppressed HG. unclosed area smaller knockdown-treated than control at nine days post-wounding, along rate deposition. levels on DNMT1 mRNA repressed knockdown HUVECs. inhibited Overexpression reversed effects CONCLUSION elevated epigenetically regulates modification impair

Language: Английский

Citations

0
New insights into N6-methyladenosine in hepatocellular carcinoma immunotherapy DOI Creative Commons

Mengran Li,

Hu Tian, Yanshuang Zhuang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

N6-methylation is a modification in which methyl group added to the adenine base of nucleotide. This crucial for controlling important functions that are vital gene expression, including mRNA splicing, stability, and translation. Due its intricate participation both normal cellular processes course disease, as well critical role determining cell fate, N6-methyladenosine (m 6 A) alteration has recently attracted lot interest. The formation progression many diseases, especially cancer, can be attributed dysregulated m A alteration, cause disturbances variety functions, such immunological responses, proliferation, differentiation. In this study, we examine how dysregulation affects hepatocellular carcinoma (HCC), with particular emphasis on it contributes evasion carcinogenesis. We also investigate potential novel therapeutic target, providing new perspectives approaches meant enhance clinical results patients HCC.

Language: Английский

Citations

0