Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, PR China.
Anhui Women and Children's Medical Center, Hefei 230001, PR China.
Life Sci. 2024 Sep 15;353:122922. doi: 10.1016/j.lfs.2024.122922. Epub 2024 Jul 18.
N6-methyladenosine (m6A) modification is closely related to cardiac fibrosis. As the most common and abundant form of mRNA modification in eukaryotes, m6A is deposited by methylases ("writers"), recognized and effected by RNA-binding proteins ("readers"), and removed by demethylases ("erasers"), achieving highly dynamic reversibility. m6A modification is involved in regulating the entire biological process of target RNA, including transcription, processing and splicing, export from the nucleus to the cytoplasm, and enhancement or reduction of stability and translation. Programmed cell death (PCD) comprises many forms and pathways, with apoptosis and autophagy being the most common. Other forms include pyroptosis, ferroptosis, necroptosis, mitochondrial permeability transition (MPT)-dependent necrosis, and parthanatos. In recent years, increasing evidence suggests that m6A modification can mediate PCD, affecting cardiac fibrosis. Since the correlation between some PCD types and m6A modification is not yet clear, this article mainly introduces the relationship between four common PCD types (apoptosis, autophagy, pyroptosis, and ferroptosis) and m6A modification, as well as their role and influence in cardiac fibrosis.
N6-甲基腺苷（m6A）修饰与心脏纤维化密切相关。作为真核生物中最常见和丰富的 mRNA 修饰形式，m6A 由甲基转移酶（“写入器”）沉积，由 RNA 结合蛋白（“读取器”）识别和作用，并由去甲基酶（“橡皮擦”）去除，实现高度动态的可逆性。m6A 修饰参与调节靶 RNA 的整个生物学过程，包括转录、加工和剪接、从核输出到细胞质、以及增强或降低稳定性和翻译。程序性细胞死亡（PCD）包括多种形式和途径，其中凋亡和自噬最为常见。其他形式包括细胞焦亡、铁死亡、坏死性凋亡、线粒体通透性转换（MPT）依赖性坏死和 Parthanatos。近年来，越来越多的证据表明 m6A 修饰可以介导 PCD，影响心脏纤维化。由于某些 PCD 类型与 m6A 修饰之间的相关性尚不清楚，本文主要介绍了四种常见的 PCD 类型（凋亡、自噬、细胞焦亡和铁死亡）与 m6A 修饰之间的关系，以及它们在心脏纤维化中的作用和影响。
