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Silencing of circRNA.2837 Plays a Protective Role in Sciatic Nerve Injury by Sponging the miR-34 Family via Regulating Neuronal Autophagy.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2018-07-25 , DOI: 10.1016/j.omtn.2018.07.011
Zhi-Bin Zhou 1 , Yu-Long Niu 2 , Gao-Xiang Huang 3 , Jia-Jia Lu 1 , Aimin Chen 1 , Lei Zhu 1
Affiliation  

Circular RNAs (circRNAs) represent a class of non-coding RNAs that are involved in transcriptional and posttranscriptional gene expression regulation and associated with different kinds of human diseases. However, the characterization and function of circular RNAs in peripheral nerve injuries remain elusive. Here, we established a rat sciatic nerve injury model and identified at least 4,942 distinct circular RNA candidates and a series of circular RNAs that were differentially expressed in injured nerve tissues compared with matched normal tissues. We characterized one frequently downregulated circular RNA, circRNA.2837, and further investigated its function in sciatic nerve injury. We found that circRNA.2837 regulated autophagy in neurons in vitro and in vivo, and downregulation of circRNA.2837 alleviated sciatic nerve injury via inducing autophagy in vivo. Mechanistically, knockdown of circRNA.2837 may protect neurons against neurological injury by acting as a sponge for members of miR-34 family. Our findings suggested that differentially expressed circular RNAs were involved in the pathogenesis of sciatic nerve injury, and circular RNAs exerted regulatory functions in sciatic nerve injury and might be used as potential targets in sciatic nerve injury therapy.



中文翻译:

通过调节神经元自噬使miR-34家族变海绵,使circRNA.2837沉默在坐骨神经损伤中起保护作用。

环状RNA(circRNA)代表一类非编码RNA,它们参与转录和转录后基因表达调控,并与不同种类的人类疾病有关。但是,环形RNA在周围神经损伤中的特征和功能仍然难以捉摸。在这里,我们建立了大鼠坐骨神经损伤模型,并鉴定了至少4,942个不同的环状RNA候选物和一系列环状RNA,这些环状RNA在受损神经组织中与匹配的正常组织相比差异表达。我们表征了一种经常下调的环状RNA circRNA.2837,并进一步研究了其在坐骨神经损伤中的功能。我们发现在神经元circRNA.2837调控自噬在体外体内和circRNA.2837的下调通过诱导自噬减轻坐骨神经损伤体内。从机制上讲,敲低circRNA.2837可能会充当miR-34家族成员的海绵,从而保护神经元免受神经损伤。我们的研究结果表明差异表达的环状RNA参与坐骨神经损伤的发病机制,并且环状RNA在坐骨神经损伤中发挥调节功能,并可能被用作坐骨神经损伤治疗的潜在靶点。

更新日期:2018-07-25
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