Comprehensive analysis of transcriptome‐wide M 6 A methylation for hepatic ischaemia reperfusion injury in mice DOI Creative Commons

Yongliang Hua,

Xinglong Li, Bing Yin

et al.

Epigenetics, Journal Year: 2023, Volume and Issue: 18(1)

Published: April 17, 2023

N6-Methyladenosine (m6A) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury different organs. However, little is known about underlying m6A-modified mRNAs hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) (RNA-seq). total, 16917 m6A peaks associated 4098 genes detected sham group, whereas 21,557 5322 group. There 909 differentially expressed peaks, 863 transcripts 516 modification determined both groups. The distribution was especially enriched coding sequence 3'UTR. Furthermore, we identified a relationship between (fold change≥1.5/≤ 0.667, p value≤0.05) change≥1.5 obtain three overlapping predicted target (Fnip2, Phldb2, Pcf11). Our study revealed transcriptome-wide map might provide theoretical basis future research terms molecular mechanisms.

Language: Английский

Activation of osteoblast ferroptosis via the METTL3/ASK1‐p38 signaling pathway in high glucose and high fat (HGHF)‐induced diabetic bone loss DOI

Youfen Lin,

Ximei Shen,

Yuzhen Ke

et al.

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(3)

Published: Feb. 1, 2022

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause-and-effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, pathophysiology diabetic yet to be clearly understood. Iron overload has been reported lead bone loss closely related osteoporosis. In this study, we hypothesized high glucose fat (HGHF) induce osteoblastic ferroptosis for pathogenesis explored possible molecular mechanisms behind. Using rat model established by HGHF feeding with subsequent intraperitoneal injection single low dose streptozocin, found serum ferritin level (a biomarker body iron store) was elevated HGHF-fed rats expression SLC7A11 GPX4 (inhibitory marker proteins ferroptosis) markedly attenuated tissue compared normal rats. an osteoblast cell model, treatment pre-osteoblastic MC3T3-E1 cells palmitic acid (HGPA) not only suppressed differentiation mineralization but also triggered ferroptosis-related death. m6A-seq revealed m6A methylation on ASK1 80.9-fold higher HGPA-treated cells. The p-ASK1 p-p38 Knockout METTL3 (methyltransferase-like 3), one major methyltransferases, abrogated HGPA-induced activation ASK1-p38 signaling pathway ferroptosis. Therefore, HGHF-induced osteoblasts main cause via METTL3/ASK1-p38 pathway, inhibition provide potential therapeutic strategy

Language: Английский

Citations

104
Chemically Modified Platforms for Better RNA Therapeutics DOI

Yesi Shi,

Xueyan Zhen,

Yiming Zhang

et al.

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

Citations

44
RNA methylations in human cancers DOI
Xiao Han, Mengke Wang, Yongliang Zhao

et al.

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 75, P. 97 - 115

Published: Nov. 19, 2020

Language: Английский

Citations

133
Epitranscriptomic editing of the RNA N6-methyladenosine modification by dCasRx conjugated methyltransferase and demethylase DOI Creative Commons

Zhen Xia,

Min Tang, Jiayan Ma

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 49(13), P. 7361 - 7374

Published: June 4, 2021

N6-methyladenosine (m6A) is a common modification on endogenous RNA transcripts in mammalian cells. Technologies to precisely modify the m6A levels at specific transcriptomic loci empower interrogation of biological functions epitranscriptomic modifications. Here, we developed bidirectional dCasRx epitranscriptome editing platform composed nuclear-localized conjugated with either methyltransferase, METTL3, or demethylase, ALKBH5, manipulate methylation events targeted sites. Leveraging this platform, specifically and efficiently edited modifications sites, reflected gene expression cell proliferation. We employed editor system elucidate molecular function m6A-binding proteins YTHDF paralogs (YTHDF1, YTHDF2 YTHDF3), revealing that YTHDFs promote m6A-mediated mRNA degradation. Collectively, our perturbation permits site-specific for delineating functional roles individual epitranscriptome.

Language: Английский

Citations

87
Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis DOI Creative Commons
Jiawei Guo, Zihao Song, Jie Yu

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(12)

Published: Dec. 26, 2022

Abstract Ischemia/reperfusion (I/R)-induced liver injury with severe cell death is a major complication of transplantation. Transmembrane member 16A (TMEM16A), component hepatocyte Ca 2+ -activated chloride channel, has been implicated in variety diseases. However, its role hepatic I/R remains unknown. Here, mice hepatocyte-specific TMEM16A knockout or overexpression were generated to examine the effect on injury. expression increased samples from patients and injury, which was correlated damage progression. Hepatocyte-specific alleviated I/R-induced mice, ameliorating inflammation ferroptotic death. showed opposite phenotype. In addition, ablation decreased inflammatory responses ferroptosis hepatocytes upon hypoxia/reoxygenation insult vitro, whereas promoted effects. The effects abolished by chemically induced ferroptosis, chemical inhibition reversed potentiated Mechanistically, interacted glutathione peroxidase 4 (GPX4) induce ubiquitination degradation, thereby enhancing ferroptosis. Disruption TMEM16A–GPX4 interaction abrogated GPX4 ubiquitination, Our results demonstrate that exacerbates promoting GPX4-dependent are therefore indispensable for TMEM16A-regulated suggesting blockades may represent promising therapeutic strategies acute

Language: Английский

Citations

41
Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation DOI Creative Commons
Shu Xu, Ya Li, Juping Chen

et al.

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(9)

Published: Sept. 30, 2020

Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. In SH-SY5Y cells and primary murine neurons, we report OGD/R accumulation of microRNA miR-422a, leading downregulation miR-422a targets myocyte enhancer factor-2D (MEF2D) mitogen-activated protein kinase 6 (MAPKK6). Ectopic inhibition attenuated OGD/R-induced cell death apoptosis, whereas overexpression induced significant apoptosis. addition, decreased expression long non-coding RNA D63785 (Lnc-D63785) regulate accumulation. Lnc-D63785 directly reversed death. downregulated through increased methyltransferase-like 3 (METTL3)-dependent m6A methylation. Conversely METTL3 shRNA methylation decrease Together, by causes

Language: Английский

Citations

67
Alteration of N6 -Methyladenosine mRNA Methylation in a Rat Model of Cerebral Ischemia–Reperfusion Injury DOI Creative Commons

Dazhuang Yi,

Qunhui Wang, Yuhao Zhao

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: March 16, 2021

This study was conducted in order to reveal the alterations N6-methyladenosine (m6A) modification profile of cerebral ischemia-reperfusion injury model rats.Rats were used establish middle artery occlusion and reperfusion (MCAO/R) model. MeRIP-seq RNA-seq performed identify differences m6A methylation gene expression. The expression regulators analyzed three datasets detected by quantitative real-time polymerase chain reaction, western blot, immunofluorescence.We identified 1,160 differentially expressed genes with hypermethylated or hypomethylated modifications. modifications involved pathways associated inflammation, while related neurons nerve synapses. Among regulators, FTO specifically localized significantly downregulated after MCAO/R.Our provided an transcriptome-wide map MACO/R rat samples, which might provide new insights into mechanisms injury.

Language: Английский

Citations

51
Amelioration of acute myocardial infarction injury through targeted ferritin nanocages loaded with an ALKBH5 inhibitor DOI
Panke Cheng,

Hukui Han,

Fuli Chen

et al.

Acta Biomaterialia, Journal Year: 2021, Volume and Issue: 140, P. 481 - 491

Published: Dec. 5, 2021

Language: Английский

Citations

48
METTL3 silenced inhibited the ferroptosis development via regulating the TFRC levels in the Intracerebral hemorrhage progression DOI
Liu Zhang, Xiangyu Wang, Wenqiang Che

et al.

Brain Research, Journal Year: 2023, Volume and Issue: 1811, P. 148373 - 148373

Published: April 25, 2023

Language: Английский

Citations

19
Dynamic RNA methylation modifications and their regulatory role in mammalian development and diseases DOI
Wenlan Yang, Yongliang Zhao, Yun‐Gui Yang

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Language: Английский

Citations

7