2. Academic Validation
  3. METTL3-Mediated m6A Modification of ISG15 mRNA Regulates Doxorubicin-Induced Endothelial Cell Apoptosis

METTL3-Mediated m6A Modification of ISG15 mRNA Regulates Doxorubicin-Induced Endothelial Cell Apoptosis

  • J Cell Mol Med. 2025 Jan;29(1):e70339. doi: 10.1111/jcmm.70339.
Dongdong Jian 1 2,  Han Li 3 4,  Chenqiu Wang 3,  Fang Li 3,  Runhua Li 3,  Shouyi Jin 3,  Jia Shen 3,  Jiamian Chen 3,  Wanjun Zhang 5,  Ling Pan 6,  Wengong Wang 1,  Hao Tang 2,  Liguo Jian 3 4,  Datun Qi 2
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
  • 2 Zhengzhou Key Laboratory of Cardiovascular Aging, Henan Province Key Laboratory for Prevention and Treatment of Coronary Heart Disease, National Health Commission key Laboratory of Cardiovascular Regenerative Medicine, Central China Fuwai Hospital of Zhengzhou University, Fuwai Central China Cardiovascular Hospital & Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, Henan, China.
  • 3 Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
  • 4 Tianjian Laboratory of Advanced Biomedical Sciences, Institute of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
  • 5 Department of Hematology, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
  • 6 Nursing Department, Haining People's Hospital (Haining Branch, the First Affiliated Hospital, Zhejiang University), Zhejiang, China.
PMID: 39789417 DOI: 10.1111/jcmm.70339
Abstract

N6-adenosine methylation (m6A) of RNA is involved in the regulation of various diseases. However, its role in chemotherapy-related vascular endothelial injury has not yet been elucidated. We found that methyltransferase-like 3 (METTL3) expression was significantly reduced during doxorubicin (DOX)-induced Apoptosis of vascular endothelial cells both in vivo and in vitro, and that silencing of METTL3 further intensified this process. Combined transcriptome and proteome Sequencing analyses revealed that the expression levels of interferon-stimulated gene 15 (ISG15) mRNA and protein significantly increased after METTL3 silencing. Methylated RNA immunoprecipitation (meRIP)-quantitative polymerase chain reaction (qPCR) and mRNA stability assays confirmed that METTL3 regulates the expression of ISG15 by methylating the 1,014,147 site on ISG15 RNA, thereby decreasing ISG15 mRNA levels. Silencing ISG15 significantly suppressed DOX-induced endothelial cell Apoptosis and dysfunction caused by METTL3 silencing. In summary, our study revealed that METTL3-mediated methylation of ISG15 mRNA is involved in DOX-induced endothelial cell Apoptosis and explored potential therapeutic targets for alleviating chemotherapy-associated vascular injury.

Keywords

ISG15; METTL3; apoptosis; doxorubicin; endothelial cell.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z