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敲低小核仁 RNA 宿主基因 10(SNHG10)通过 miR-1277-5p/胰岛素底物受体 2 轴减轻人神经母细胞瘤细胞的损伤。

Knockdown of small nucleolar RNA host gene 10 (SNHG10) alleviates the injury of human neuroblastoma cells via the miR-1277-5p/insulin substrate receptor 2 axis.

机构信息

Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong, China.

出版信息

Bioengineered. 2022 Jan;13(1):709-720. doi: 10.1080/21655979.2021.2012623.

Abstract

Parkinson's disease is a common neurodegenerative disease with a complex physio-pathology. So far, there is no effective medical strategies to prevent the progression of Parkinson's disease. Understanding the mechanisms underlying the progression of Parkinson's disease could provide insights into the formulation of novel preventative or treatment strategies. Small nucleolar RNA host gene 10 (SNHG10) is a lncRNA which has been implicated in the development of many cancers. However, its potential role in Parkinson's disease remains unknown. In this study, we found that SNHG10 was upregulated while miR-1277-5p was downregulated in the Parkinson's disease cell model of 1-Methyl-4-phenyl-pyridine ion (MPP+) induced SH-SY5Y cells. We further revealed that SNHG10 sponged miR-1277-5p to negatively regulate its expression, and miR-1277-5p could bind to the 3'UTR of insulin substrate receptor 2 (IRS2) mRNA to suppress its expression. These data suggest that SNHG10 regulates IRS2 through interacting with miR-1277-5p in the cell model of Parkinson's disease. Through a series of molecular experiments and functional assays, we demonstrated that downregulating SNHG10 in the cell model of Parkinson's disease attenuated the cell injury by reducing the expression of IRS2. Meanwhile, inhibiting miR-1277-5p or overexpressing IRS2 could partially reverse the effect of SNHG10 knockdown. In summary, our data indicate that knockdown of SNHG10 mitigates MPP induced damage in SH-SY5Y cells via the miR-1277-5p/IRS2 axis.

摘要

帕金森病是一种常见的神经退行性疾病,其病理生理学机制复杂。目前,尚无有效的医学策略来阻止帕金森病的进展。了解帕金森病进展的机制可以为制定新的预防或治疗策略提供思路。小核仁 RNA 宿主基因 10(SNHG10)是一种长链非编码 RNA,它与许多癌症的发生发展有关。然而,其在帕金森病中的作用尚不清楚。在本研究中,我们发现 SNHG10 在 1-甲基-4-苯基-1,2,3,6-四氢吡啶离子(MPP+)诱导的 SH-SY5Y 细胞帕金森病细胞模型中上调,而 miR-1277-5p 下调。我们进一步揭示 SNHG10 可以通过海绵吸附 miR-1277-5p 来负调控其表达,miR-1277-5p 可以结合胰岛素底物受体 2(IRS2)mRNA 的 3'UTR 来抑制其表达。这些数据表明,SNHG10 通过与帕金森病细胞模型中的 miR-1277-5p 相互作用来调节 IRS2。通过一系列分子实验和功能测定,我们证明了在帕金森病细胞模型中下调 SNHG10 可以通过降低 IRS2 的表达来减轻细胞损伤。同时,抑制 miR-1277-5p 或过表达 IRS2 可以部分逆转 SNHG10 敲低的作用。综上所述,我们的数据表明,下调 SNHG10 通过 miR-1277-5p/IRS2 轴减轻 MPP 诱导的 SH-SY5Y 细胞损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea43/8805890/dc78086a6390/KBIE_A_2012623_F0001_OC.jpg

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