METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2–dependent mechanism DOI Creative Commons
Xiaoxue Hou, Yuwen Li, Jiali Song

и другие.

Hepatology Communications, Год журнала: 2023, Номер 7(8)

Опубликована: Авг. 1, 2023

Background: N 6 -methyladenosine (m A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated response to a wide range of physiological and pathological states. Nonetheless, involvement METTL14-induced m A liver fibrosis (LF) has yet be established. Methods: In vitro, HSC cell lines with knock-down overexpression METTL14 were constructed, effects gene on phenotypic function activated HSCs observed. The proliferation rate was measured by CCK8 EDU, cycle flow detector, migration Transwell, contractility F-actin observed after phalloidin staining. downstream target NOVA2 screened combined sequencing MeRIP-seq RNA-seq, signal analysis. Adeno-associated virus (AAV) injected into tail vein vivo knock down expression METTL14, so as further observe role progress LF. Results: our research showed that methylase content decreased hepatic tissue from patients LF, leading lowered degree modification. Functionally, we discovered knocking methyltransferase led increased activation substantial worsening Mechanically, shown multiomics study HSCs, depleting levels deposition onNOVA2 mRNA transcripts, which prompted YTHDF2 detect degrade decrease Conclusions: functioned profibrotic suppressing activity mechanism dependent A-YTHDF2. Moreover, exacerbated while prevented its development partly reversed damage.

Язык: Английский

Histone demethylases in the regulation of immunity and inflammation DOI Creative Commons
Lihua Qu, Tong Yin,

Yijin Zhao

и другие.

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Июнь 23, 2023

Abstract Pathogens or danger signals trigger the immune response. Moderate response activation removes pathogens and avoids excessive inflammation tissue damage. Histone demethylases (KDMs) regulate gene expression play essential roles in numerous physiological processes by removing methyl groups from lysine residues on target proteins. Abnormal of KDMs is closely associated with pathogenesis various inflammatory diseases such as liver fibrosis, lung injury, autoimmune diseases. Despite becoming exciting targets for diagnosing treating these diseases, role enzymes regulation still unclear. Here, we review underlying mechanisms through which immune-related pathways responses. In addition, also discuss future applications inhibitors

Язык: Английский

Процитировано

31
The emerging importance role of m6A modification in liver disease DOI Open Access

Sheng Wang,

Songsen Gao,

Wufei Ye

и другие.

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 162, С. 114669 - 114669

Опубликована: Апрель 8, 2023

N6-methyladenosine (m6A) modification, as one of the most common types inner RNA modification in eukaryotes, plays a multifunctional role normal and abnormal biological processes. This type is modulated by m6A writer, eraser reader, which turn impact various processes metabolism, such processing, translation, nuclear export, localization decay. The current academic view holds that exerts crucial post-transcriptional modulation gene expression, involved multiple cellular functions, developmental disease However, potential molecular mechanism specific development liver have not been fully elucidated. In our review, we summarized latest research progress on disease, explored how these novel findings reshape knowledge metabolism. addition, also illustrated effect regeneration to prompt further exploration physiology pathology, providing new insights references for search therapeutic targets disease.

Язык: Английский

Процитировано

30
PXR Activation Relieves Deoxynivalenol‐Induced Liver Oxidative Stress Via Malat1 LncRNA m6A Demethylation DOI Creative Commons
Yue Feng, Jiakun Shen, Zishen Lin

и другие.

Advanced Science, Год журнала: 2024, Номер 11(25)

Опубликована: Апрель 24, 2024

Abstract Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, unique role of xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON‐induced stress investigated. Treatment with PXR agonist 3‐indole‐propionic acid (IPA) alleviates injury both vitro vivo. Mechanistically, it discovered for first time that IPA directly transactivates m 6 A demethylase FTO expression, leading to site‐specific demethylation decreased abundance YTHDC1‐bound Malat1 lncRNA at single‐nucleotide resolution. The diminished modification reduces its stability augments antioxidant pathways governed by NRF2, consequently mitigating injury. Furthermore, knockout mice exhibit injury, emphasizing Collectively, findings establish PXR‐mediated A‐dependent expression determines hepatocyte via FTO, providing valuable insights into potential offers strategies treatment.

Язык: Английский

Процитировано

13
Hyodeoxycholic acid ameliorates cholestatic liver fibrosis by facilitating m6A-regulated expression of a novel anti-fibrotic target ETV4 DOI
Xiaoyong Xue, Runping Liu,

Yajie Cai

и другие.

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

2
DNA 5mC and RNA m6A modification successively facilitates the initiation and perpetuation stages of HSC activation in liver fibrosis progression DOI Creative Commons
Yue Feng, Shihui Guo, Yulan Zhao

и другие.

Cell Death and Differentiation, Год журнала: 2023, Номер 30(5), С. 1211 - 1220

Опубликована: Фев. 25, 2023

Язык: Английский

Процитировано

21
Gastric cancer-derived LBP promotes liver metastasis by driving intrahepatic fibrotic pre-metastatic niche formation DOI Creative Commons
Li Xie, Shengkui Qiu, Lu Chen

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Окт. 3, 2023

Liver metastasis (LM) is one of the most common distant metastases gastric cancer (GC). However, mechanisms underlying LM GC (GC-LM) remain poorly understood. This study aimed to identify tumour-secreted protein associated with GC-LM and investigate by which this secreted remodels liver microenvironment promote GC-LM.Data-independent acquisition mass spectrometry (DIA-MS), mRNA expression microarray, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) immunohistochemistry (IHC) were performed validate GC-secreted proteins GC-LM. A modified intrasplenic injection mouse model was used evaluate progression tumour burden in vivo. Flow cytometry, immunofluorescence (IF), western blots (WB) IHC pre-metastatic niche (PMN) formation pre-modelling models. sequencing PMA-treated THP-1 cells or without lipopolysaccharide binding (LBP) treatment functional target genes LBP macrophages. Co-immunoprecipitation (Co-IP), WB, ELISA, IF Transwell assays explore mechanism inducing intrahepatic PMN formation.LBP identified as a critical correlated worse prognosis patients GC. activated TLR4/NF-κB pathway TGF-β1 secretion macrophages, which, turn, hepatic satellite (HSCs) direct fibrotic formation. Additionally, enhanced migration invasion incoming metastatic liver. Consequently, selective targeting TGF-β/Smad signaling galunisertib demonstrated its efficacy effectively preventing vivo.The results provide compelling evidence that serological can serve valuable diagnostic biomarker for early detection Mechanistically, GC-derived mediates crosstalk between primary promoting induces Importantly, selectively represents promising preventive therapeutic strategy

Язык: Английский

Процитировано

19
Regulatory roles of N6-methyladenosine (m6A) methylation in RNA processing and non-communicable diseases DOI
Faiz Ali Khan, Bernard Nsengimana, Usman Ayub Awan

и другие.

Cancer Gene Therapy, Год журнала: 2024, Номер unknown

Опубликована: Июнь 5, 2024

Язык: Английский

Процитировано

9
STUB1 is acetylated by KAT5 and alleviates myocardial ischemia-reperfusion injury through LATS2-YAP-β-catenin axis DOI Creative Commons
Can Liu,

Zhongxuan Gui,

Cheng An

и другие.

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Апрель 1, 2024

Abstract Myocardial ischemia-reperfusion injury (MIRI) is involved in the pathogenesis of multiple cardiovascular diseases. This study elucidated biological function lysine acetyltransferase 5 (KAT5) cardiomyocyte pyroptosis during MIRI. Oxygen-glucose deprivation/reoxygenation and left anterior descending coronary artery ligation were used to establish MIRI models. Here we show, KAT5 STIP1 homology U-box-containing protein 1 (STUB1) downregulated, while large tumor suppressor kinase 2 (LATS2) was upregulated KAT5/STUB1 overexpression or LATS2 silencing repressed pyroptosis. Mechanistically, promoted STUB1 transcription via acetylation modulation, subsequently caused ubiquitination degradation LATS2, which activated YAP/β-catenin pathway. Notably, inhibitory effect on abolished by depletion. Our findings suggest that inhibits NLRP3-mediated relieve through modulation STUB1/LATS2/YAP/β-catenin axis, providing a potential therapeutic target for

Язык: Английский

Процитировано

8
Quercetin attenuated necroptosis and apoptosis caused by LPS-induced mitochondrial function dysfunction through the METTL3-mediated PTEN m6A methylation/PI3K/AKT signaling in broiler livers DOI
Xia Yu, Yidan Wang, Kai Chen

и другие.

Phytomedicine, Год журнала: 2025, Номер 139, С. 156551 - 156551

Опубликована: Фев. 22, 2025

Язык: Английский

Процитировано

1
RNA modifications in the progression of liver diseases: from fatty liver to cancer DOI Creative Commons
Simiao Li‐Sauerwine, Wajahat Z. Mehal, Xinshou Ouyang

и другие.

Science China Life Sciences, Год журнала: 2024, Номер 67(10), С. 2105 - 2119

Опубликована: Май 27, 2024

Abstract Non-alcoholic fatty liver disease (NAFLD) has emerged as a prominent global health concern associated with high risk of metabolic syndrome, and impacted substantial segment the population. The spectrum ranges from simple to non-alcoholic steatohepatitis (NASH), which can progress cirrhosis hepatocellular carcinoma (HCC) is increasingly becoming prevalent indication for transplantation. existing therapeutic options NAFLD, NASH, HCC are limited, underscoring urgent need innovative treatment strategies. Insights into gene expression, particularly RNA modifications such N 6 methyladenosine (m A), hold promising avenues interventions. These play integral roles in metabolism cellular functions, encompassing entire NAFLD-NASH-HCC progression. This review will encompass recent insights on diverse modifications, including m A, pseudouridine (ψ), 1 -methyladenosine 5-methylcytidine 5 C) across various species. It uncover their significance crucial aspects steatosis, inflammation, fibrosis, tumorigenesis. Furthermore, prospective research directions implications be explored, advancing our comprehensive understanding intricate interconnected nature these pathological conditions.

Язык: Английский

Процитировано

6