The lncRNA MALAT1/miR-30/Spastin Axis Regulates Hippocampal Neurite Outgrowth.
The lncRNA MALAT1/miR-30/Spastin Axis Regulates Hippocampal Neurite Outgrowth.
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lncRNA MALAT1/miR-30/Spastin 轴调节海马神经突生长
DOI：
10.3389/fncel.2020.555747
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发表时间：
2020
影响因子：
5.3
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Jiang T;Cai Z;Ji Z;Zou J;Liang Z;Zhang G;Liang Y;Lin H;Tan M
Spastin是一种微管切割酶，对神经突生长非常重要。然而，在微管相关的过程中，spastin的转录后调控机制在很大程度上是未知的。我们证明了在神经突生长过程中，spastin的表达水平受到长的非编码RNA（lncRNA）转移相关的肺腺癌转录本1（MALAT 1）/microRNA-30（miR-30）轴的控制。随着培养天数的增加，海马神经元中miR-30的表达水平降低，miR-30过表达受到抑制，而miR-30抑制则促进海马神经元的突起生长。使用荧光素酶报告基因测定验证Spastin作为miR-30的靶基因。过表达miR-30模拟物可抑制蛋白质表达、微管切断活性和痉挛素的轴突促进作用，而miR-30抑制剂可增加痉挛素的作用。MALAT 1表达在神经突生长过程中增加，MALAT 1沉默损害神经突生长。miR-30是MALAT 1的海绵靶点，MALAT 1/miR-30改变海马神经元中的神经突生长。MALAT 1过表达逆转了miR-30对含有spastin的荧光素酶报告基因构建体的活性以及spastin mRNA和蛋白表达的抑制作用，表明spastin是MALAT 1/miR-30的下游效应子。MALAT 1/miR-30级联还调节spastin诱导的微管切断，并且MALAT 1/miR-30/spastin轴调节海马神经元中的神经突生长。这项研究提出了一种新的机制，涉及MALAT 1/miR-30调节痉挛蛋白表达的海马神经元轴突生长。
Spastin, a microtubule-severing enzyme, is important for neurite outgrowth. However, the mechanisms underlying the post-transcriptional regulation of spastin during microtubule-related processes are largely unknown. We demonstrated that the spastin expression level is controlled by a long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-30 (miR-30) axis during neurite outgrowth. The miR-30 expression level decreased in hippocampal neurons with increasing days in culture, and miR-30 overexpression suppressed while miR-30 inhibition promoted neurite outgrowth in hippocampal neurons. Spastin was validated as a target gene of miR-30 using the luciferase reporter assay. The protein expression, microtubule severing activity, and neurite promoting effect of spastin were suppressed by the overexpression of miR-30 mimics and increased by miR-30 inhibitors. MALAT1 expression increased during neurite outgrowth and MALAT1 silencing impaired neurite outgrowth. miR-30 was a sponge target of MALAT1 and MALAT1/miR-30 altered neurite outgrowth in hippocampal neurons. MALAT1 overexpression reversed the inhibitory effect of miR-30 on the activity of a luciferase reporter construct containing spastin, as well as spastin mRNA and protein expression, indicating that spastin was a downstream effector of MALAT1/miR-30. The MALAT1/miR-30 cascade also modulated spastin-induced microtubule severing, and the MALAT1/miR-30/spastin axis regulated neurite outgrowth in hippocampal neurons. This study suggests a new mechanism governing neurite outgrowth in hippocampal neurons involving MALAT1/miR-30-regulated spastin expression.
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影响因子：
3.7
作者：
Eguchi T;Watanabe K;Hara ES;Ono M;Kuboki T;Calderwood SK
通讯作者：
Calderwood SK
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
3
作者：
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通讯作者：
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影响因子：
3.3
作者：
Jiang, Tao;Zhang, Guowei;Tan, Minghui
通讯作者：
Tan, Minghui
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影响因子：
5.3
作者：
Chen L;Feng P;Zhu X;He S;Duan J;Zhou D
通讯作者：
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