Silencing of circRNA.2837 Plays a Protective Role in Sciatic Nerve Injury by Sponging the miR-34 Family via Regulating Neuronal Autophagy.
Silencing of circRNA.2837 Plays a Protective Role in Sciatic Nerve Injury by Sponging the miR-34 Family via Regulating Neuronal Autophagy.
复制标题
circRNA.2837 的沉默通过调节神经元自噬来海绵 miR-34 家族，从而在坐骨神经损伤中发挥保护作用。
DOI：
10.1016/j.omtn.2018.07.011
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发表时间：
2018-09-07
期刊：
影响因子：
--
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Zhou ZB;Niu YL;Huang GX;Lu JJ;Chen A;Zhu L
Circular RNA（circRNA）是一类参与转录和转录后基因表达调控的非编码RNA，与多种人类疾病相关。然而，环状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，并确定了至少4，942个不同的环状RNA候选物和一系列环状RNA，这些环状RNA在损伤的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，circRNA.2837在体外和体内调节神经元中的自噬，并且下调circRNA.2837通过诱导体内自噬减轻坐骨神经损伤。在机制上，敲低circRNA.2837可以通过充当miR-34家族成员的海绵来保护神经元免受神经损伤。结果提示，差异表达的环状RNA参与了坐骨神经损伤的发病机制，环状RNA在坐骨神经损伤中具有调节作用，有可能成为坐骨神经损伤治疗的潜在靶点。
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.
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