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在叶酸缺乏引起的神经管缺陷中,CircRNA-关联的CeRNA网络的表征

Shan Wang¹, Yu Bing Zeng², Pei Pei²

¹Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China;Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing 100020, China;Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China.

Biomedical and environmental sciences : BES

|October 7, 2023

概括

循环RNAs (circRNAs) 在神经管缺陷 (NTDs) 中发挥作用. Circzfp644具有竞争性地结合miR-20-5p,增加Gas7表达,这是一个涉及NTD病变的机制.

科学领域:

分子生物学分子生物学
发展生物学发展生物学
遗传学是一个遗传学.

背景情况:

循环RNAs (circRNAs) 越来越多地被认为是它们在疾病病理学中的作用.
神经管缺陷 (NTD) 是常见的先天性异常,具有复杂的病因.
了解NTD背后的分子机制对于开发诊断和治疗策略至关重要.

研究的目的:

研究circRNAs在神经管缺陷 (NTDs) 病变发生过程中的参与.
描述与NTD相关的circRNA-ceRNA网络.
阐明Circzfp644,miR-20-5p和Gas7在NTD发展中的特定作用.

主要方法:

高通量测序用于识别低叶酸诱导的NTD小鼠脑组织中的失调的circRNAs,miRNAs和mRNAs.
通过RT-PCR和纳米链测试,验证小鼠和人类NTD组织中关键分子的表达水平.
在体外实验中使用miRNA模仿剂/抑制剂和光酶试验来确定Circzfp644,miR-20-5p和Gas7.7之间的功能相互作用.

主要成果:

在NTD脑组织中观察到57个circRNAs,16个miRNAs和148个mRNAs的显著失调.
Circzfp644通过与miR-20-5p结合,充当竞争的内源RNA (ceRNA),从而增加其目标基因Gas7.7的表达.
在人类NTD组织中检测到Circzfp644和Gas7的下调,以及miR-20-5p的上调.

结论:

这项研究确定了一种新的circRNA介导的调节途径,涉及Circzfp644,miR-20-5p和Gas7在NTD的背景下.
这些发现为神经系统发育和NTD病变的分子机制提供了新的见解.
循环RNAs代表神经管缺陷的潜在诊断生物标志物和治疗点.

关键词:

圆周64444的时间叶酸缺乏症叶酸缺乏症气体7 气体7 气体 NTDs 是一个NTD.在 miR-20-5p 中使用.

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