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在缺血性心力衰竭患者中,circRNA-miRNA-mRNA放松调节网络
Alisia Madè1, Alessia Bibi1,2, Jose Manuel Garcia-Manteiga3
1Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy.
Cells
|November 10, 2023
概括
循环RNAs (circRNAs) 作为miRNA海绵,形成竞争的内源RNA (ceRNA) 网络,调节心血管疾病. 这项研究确定了缺血性心力衰竭 (IHF) 中的circRNA-ceRNA网络,揭示了circBPTFTF.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 心血管研究研究心血管研究
背景情况:
- 非编码RNAs (ncRNAs),包括循环RNAs (circRNAs) 和微RNAs (miRNAs),是心血管疾病 (CVD) 的关键调节者.
- 循环RNAs可以通过海绵miRNAs作为竞争的内源RNAs (ceRNAs) 发挥作用,从而调节miRNA目标mRNA水平.
- 缺血性心力衰竭 (IHF) 中的作用和特定的circRNA-ceRNA网络在很大程度上仍未被描述.
研究的目的:
- 在非末期缺血性心力衰竭 (IHF) 中识别circRNA中心的ceRNA网络.
- 实验验证一个特定的circRNA-miRNA-mRNA相互作用网络.
- 为了研究circRNAs在IHF病变发生中的功能作用.
主要方法:
- 生物信息学分析与实验数据相结合,以确定circRNA-miRNA-mRNA相互作用.
- KEGG路径分析以确定已识别的mRNA标的功能丰富.
- 实验验证包括circRNA拉下测试,circRNA沉默和内皮细胞和患者样本表达分析.
主要成果:
- 确定了大约662个circRNA-miRNA-mRNA相互作用,与丰富的mRNA映射到与心血管疾病相关的途径.
- 一个以circBPTF为中心的ceRNA网络经过实验验证,显示与let-7a-5p,miR-18a-3p,miR-146b-5p和miR-196b-5p的相互作用.
- circBPTF沉默影响了miR-196b-5p标 (HDAC9,LRRC17) 的表达,并诱导了内皮细胞循环停止. 在缺氧内皮细胞和IHF患者的心脏中,circBPTF表达被上调.
结论:
- circRNAs作为miRNA海绵起作用,形成ceRNA网络,调节mRNA点并影响IHF病变发生.
- 已识别的circBPTF ceRNA网络在内皮细胞功能中发挥作用,并在IHF上调节.
- 这些发现为HF病原发生提供了新的见解,并为未来的研究提供了基础.
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