通过调节m6A甲基化修饰的miR-320a,METTL3加速了葡萄球菌蛋白A (SpA) 诱导的骨髓炎的进展
Ding Gao1, Jian Shi2, Siyu Lu2
1Department of Orthopedic Trauma Surgery, Meizhou People's Hospital, Meizhou, 514031, China.
Journal of orthopaedic surgery and research
|November 7, 2024
概括
甲基转移酶样3 (METTL3) 通过控制m6A/miR-320a/PIK3CA轴来调节骨髓炎 (OM) 的骨质稳态. 沉默METTL3通过减轻炎症和氧化应激来缓解OM的发展.
科学领域:
- 分子生物学分子生物学
- 生物化学 生化学
- 免疫学 免疫学 免疫学
背景情况:
- 骨髓炎 (OM) 是一种破坏恒温的骨感染,通常是由金黄色葡萄球菌 (SA) 引起的.
- N6-甲基氨酸 (m6A) 调节剂与OM有关,但它们的确切作用尚不清楚.
- 甲基转移酶样3 (METTL3) 是本研究中调查的关键m6A调节剂.
研究的目的:
- 调查METTL3介导的m6A修饰在骨髓炎发展中的作用.
- 阐明涉及METTL3,miR-320a和PIK3CA在SA诱导的骨损伤中的分子机制.
主要方法:
- 人类骨介质干细胞 (hBMSCs) 用葡萄球菌蛋白A (SpA) 进行治疗,以模拟OM.
- 分析了METTL3表达,骨质分化,氧化应激和炎症反应.
- 功能性测试涉及METTL3淘汰,miR-320a模仿和PIK3CA操纵.
主要成果:
- 在OM患者和接受SPA治疗的hBMSC患者中,METTL3的调节升高,加剧了骨质生成抑制,氧化应激和炎症.
- 降低METTL3改善了SPA诱导的损伤,而miR-320a模仿器逆转了这些保护作用.
- 确定了miR-320a/PIK3CA轴作为一个由METTL3.3规范的关键下游路径.
结论:
- 在OM中,METTL3/m6A/miR-320a/PIK3CA轴在调节骨质分化,氧化应激和炎症方面发挥着关键作用.
- 准METTL3/m6A通路为骨髓炎提供了一个潜在的治疗策略.
相关概念视频
Role of Matrix Metalloproteases in Degradation of ECM
2.3K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
MicroRNAs
3.0K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.0K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Translational Regulation
1
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
1


