MicroRNA-20b-5p aggravates neuronal apoptosis induced by β-Amyloid via down-regulation of Ras homolog family member C in Alzheimer's disease
| Autor: | Jie Guo, Zhu Tian, Qian Dong, Tongrui Wu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
RhoC Down-Regulation Apoptosis Mice Transgenic Hippocampus PC12 Cells Flow cytometry 03 medical and health sciences Mice 0302 clinical medicine Western blot Downregulation and upregulation Alzheimer Disease microRNA medicine Animals Viability assay Neurons Gene knockdown Amyloid beta-Peptides biology medicine.diagnostic_test Chemistry General Neuroscience Peptide Fragments Rats MicroRNAs 030104 developmental biology biology.protein Cancer research 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience letters. 742 |
| ISSN: | 1872-7972 |
| Popis: | Recent studies have reported that microRNAs are abnormally expressed in brain tissues of Alzheimers disease (AD) patients. However, the accurate function of miR-20b-5p in AD has not been elucidated. We intended to investigate the role and underlying mechanism of miR-20b-5p in AD. The expression of miR-20b-5p was increased, and the expression of RhoC was decreased in the hippocampus of Appswe/PS△E 9 mice. In order to construct a cell model in vitro to study the underlying action mechanism, PC12 cells were treated with Aβ25-35. The cell apoptosis detected by flow cytometry and the expression of cleaved-caspase-3 detected by western blot were both remarkably increased in PC12 cells treated with Aβ25-35, but they were reduced by miR-20b-5p inhibitor. In addition, MTT test showed that the cell survival rate in Aβ25-35 + miR-20b-5p inhibitor group was higher than that in Aβ25-35 + NC inhibitor group. Double luciferase reporter gene analysis confirmed that the binding site of miR-20b-5p was in 3'- UTR of RhoC mRNA. Knockdown of RhoC increased neuronal apoptosis induced by Aβ25-35 and the expression of cleaved-caspase-3, while miR-20b-5p inhibitor reversed these effects. Knockdown of RhoC aggravated the inhibition effect on cell viability induced by Aβ25-35, while miR-20b-5p inhibitor diminished these effects. In conclusion, inhibition of miR-20b-5p attenuates apoptosis induced by Aβ25-35 in PC12 cells through targeting RhoC. Therefore, miR-20b-5p may be a perspective curative target for AD. |
| Databáze: | OpenAIRE |
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