Methyltransferase like‐14 suppresses growth and metastasis of non‐small‐cell lung cancer by decreasing LINC02747 DOI Creative Commons
Jiemin Wang, Shu Wang, Haopeng Yang

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: 115(9), P. 2931 - 2946

Published: June 18, 2024

Abstract Multiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions impact of diverse modifications on gene expression cancer is crucial for development precision medicine. We found that methyltransferase‐like 14 (METTL14) was significantly downregulated non‐small‐cell lung (NSCLC) tissues. Functional experiments demonstrated overexpression METTL14 inhibited proliferation migration NSCLC cells both vivo vitro, colorimetric m 6 A quantification assay also showed knockdown notably reduced global modification levels cells. By using methylated‐RNA immunoprecipitation‐qPCR dual‐luciferase reporter assays, we verified long noncoding RNA LINC02747 a target regulated by METTL14‐mediated modification, silencing malignant progression modulating PI3K/Akt CDK4/Cyclin D1 signaling pathway. Further studies revealed promoted methylation accelerated decay mRNA via increased recognition “GAACU” binding site YTHDC2. Additionally, histone demethylase lysine‐specific 5B (KDM5B) mediated demethylation H3 lysine 4 tri‐methylation (H3K4me3) promoter region repressed its transcription. In summary, KDM5B at transcriptional level H3K4me3‐dependent manner, while modulated modification. Our results demonstrate synergy multiple regulating phenotype NSCLC, revealing complex regulation involved occurrence cancer.

Language: Английский

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

5
METTL14 modulates the progression and ferroptosis of colitis by regulating the stability of m6A-modified GPX4 DOI Creative Commons
Yuhua Chen, Weiguo Fan, Ying Lyu

et al.

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Feb. 8, 2025

Ulcerative colitis (UC) is non-specific inflammatory bowel disease. UC development and progression were closely associated with epigenetic modifications. Nevertheless, the specific relationship between N6-methyladenosine (m6A) modification at RNA transcription levels pathogenesis remains unclear. We established cell models mouse through dextran sulfate sodium (DSS) induction. The expression of METTL14 analyzed via qRT-PCR western blot. In vitro functional experiments evaluated effects overexpression on viability DSS-induced NCM460 cells ferroptosis markers. Use m6A methylation detection kit, MeRIP-qPCR, stability confirmed molecular mechanism controlled by METTL14. vivo mice elucidated interaction GPX4. Findings from this study indicated a notable reduction in methyltransferase models. effectively suppressed cells. addition, enhanced GPX4 mRNA mediating modification, interplay introduced innovative therapeutic approaches for management.

Language: Английский

Citations

0
Research progress on N6-methyladenosine and non-coding RNA in multiple myeloma DOI Creative Commons
Xiaoqi Sun,

Yongming Zhou,

Wenwei Zhu

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 25, 2025

N6-methyladenosine (m6A) and non-coding RNA (ncRNA) play important roles in the occurrence, development, prognosis of multiple myeloma (MM). They not only affect stemness, growth, apoptosis MM cells but also intervene proliferation, migration, invasion, even drug resistance. It is a prognostic factor for poor survival. Therefore, in-depth research on mechanisms m6A ncRNA significant diagnosis, treatment, MM.

Language: Английский

Citations

0
N6-methyladenosine-modified circ_0000517 promotes non-small cell lung cancer metastasis via miR-1233-3p/CDH6 axis DOI

Weixian Lin,

Lifang Huang,

Zhu’an Ou

et al.

Journal of Molecular Histology, Journal Year: 2025, Volume and Issue: 56(3)

Published: April 25, 2025

Language: Английский

Citations

0
Methyltransferase like‐14 suppresses growth and metastasis of non‐small‐cell lung cancer by decreasing LINC02747 DOI Creative Commons
Jiemin Wang, Shu Wang, Haopeng Yang

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: 115(9), P. 2931 - 2946

Published: June 18, 2024

Abstract Multiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions impact of diverse modifications on gene expression cancer is crucial for development precision medicine. We found that methyltransferase‐like 14 (METTL14) was significantly downregulated non‐small‐cell lung (NSCLC) tissues. Functional experiments demonstrated overexpression METTL14 inhibited proliferation migration NSCLC cells both vivo vitro, colorimetric m 6 A quantification assay also showed knockdown notably reduced global modification levels cells. By using methylated‐RNA immunoprecipitation‐qPCR dual‐luciferase reporter assays, we verified long noncoding RNA LINC02747 a target regulated by METTL14‐mediated modification, silencing malignant progression modulating PI3K/Akt CDK4/Cyclin D1 signaling pathway. Further studies revealed promoted methylation accelerated decay mRNA via increased recognition “GAACU” binding site YTHDC2. Additionally, histone demethylase lysine‐specific 5B (KDM5B) mediated demethylation H3 lysine 4 tri‐methylation (H3K4me3) promoter region repressed its transcription. In summary, KDM5B at transcriptional level H3K4me3‐dependent manner, while modulated modification. Our results demonstrate synergy multiple regulating phenotype NSCLC, revealing complex regulation involved occurrence cancer.

Language: Английский

Citations

3