MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells.,FEBS Open Bio

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MAST1 modulates neuronal differentiation and cell cycle exit via P27 in neuroblastoma cells.
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-04-29 , DOI: 10.1002/2211-5463.12860
Tianrui Jing ₁ , Jing Ma ₂ , Huanqiang Zhao ₃ , Jin Zhang ₁ , Nan Jiang ₁ , Duan Ma _{1,

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Affiliation

Although 19p13.13 microdeletion syndrome has been consistently associated with intellectual disability, overgrowth, and macrocephaly, the underlying mechanisms remain unclear. MAST1, a member of the microtubule‐associated serine/threonine kinase family, has been suggested as a potential candidate gene responsible for neurologic abnormalities in 19p13.13 microdeletion syndrome, but its role in nervous system development remains to be elucidated. Here, we investigated how MAST1 contributes to neuronal development. We report that MAST1 is upregulated during neuronal differentiation of the human neuroblastoma cell line, SH‐SY5Y. Inhibition of MAST1 expression by RNA interference attenuated neuronal differentiation of SH‐SY5Y cells. Cell cycle analyses revealed that MAST1‐depleted cells did not undergo cell cycle arrest after RA treatment. Consistent with this observation, the number of EdU‐positive cells significantly increased in MAST1 knockdown cells. Intriguingly, levels of P27, a cyclin‐dependent kinase inhibitor, were also increased during neuronal differentiation, and MAST1 knockdown reduced the expression of P27. Moreover, reduced neuronal differentiation caused by MAST1 depletion was rescued partially by P27 overexpression in SH‐SY5Y cells. Collectively, these results suggest that MAST1 influences nervous system development by affecting neuronal differentiation through P27.

中文翻译：

MAST1 通过神经母细胞瘤细胞中的 P27 调节神经元分化和细胞周期退出。

尽管 19p13.13 微缺失综合征一直与智力障碍、过度生长和巨头畸形有关，但其潜在机制仍不清楚。MAST1 是微管相关丝氨酸/苏氨酸激酶家族的成员，已被认为是导致 19p13.13 微缺失综合征神经系统异常的潜在候选基因，但其在神经系统发育中的作用仍有待阐明。在这里，我们研究了 MAST1 如何促进神经元发育。我们报告说 MAST1 在人神经母细胞瘤细胞系 SH-SY5Y 的神经元分化过程中被上调。通过 RNA 干扰抑制 MAST1 表达减弱了 SH-SY5Y 细胞的神经元分化。细胞周期分析显示 MAST1 耗尽的细胞在 RA 治疗后没有发生细胞周期停滞。与这一观察结果一致，MAST1 敲低细胞中 EdU 阳性细胞的数量显着增加。有趣的是，P27（一种细胞周期蛋白依赖性激酶抑制剂）的水平在神经元分化过程中也增加，MAST1 敲低降低了 P27 的表达。此外，SH-SY5Y 细胞中 P27 过表达部分挽救了由 MAST1 耗竭引起的神经元分化减少。总的来说，这些结果表明 MAST1 通过 P27 影响神经元分化来影响神经系统发育。SH-SY5Y细胞中的P27过表达部分挽救了由MAST1耗竭引起的神经元分化减少。总的来说，这些结果表明 MAST1 通过 P27 影响神经元分化来影响神经系统发育。SH-SY5Y细胞中的P27过表达部分挽救了由MAST1耗竭引起的神经元分化减少。总的来说，这些结果表明 MAST1 通过 P27 影响神经元分化来影响神经系统发育。

更新日期：2020-04-29

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