Effects of microRNA-137, regulated by long non-coding RNA growth arrest-specific 5, on Aβ-induced hippocampal neuronal damage in rats
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Department of Geriatrics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China

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R-33

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    Abstract:

    Objective To investigate the effects of microRNA (miR)-137, regulated by long non-coding RNA (LncRNA) growth arrest-specific 5 ( GAS5 ), on amyloid-β ( Aβ)-induced hippocampal neuronal damage in rats. Methods Rats were divided into the control group, Aβ group, Aβ+Si-NC group, Aβ+si-GAS5 group, Aβ+si-GAS5+ anti-miR-NC group and Aβ+si-GAS5+anti-miR-137 group (n= 10 rats per group). The Y maze was used to detect learning and memory in rats. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of GAS5 and miR-137 in the hippocampal CA1 area. The protein levels of B-lymphoma-2 gene (Bcl2), Bcl2-related X protein (BAX), caspase-3 were detected by Western blot and neuronal morphology was observed using Nissl staining. In addition, terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel) staining was used to observe neuronal apoptosis and the relationship between miR-137 and GAS5 was identified using double luciferase. Results Compared with the control group, the levels of GAS5 mRNA, BAX, caspase-3 protein, neuronal mortality, and neuronal apoptosis rate were higher in the Aβ and Aβ+Si-NC groups (P<0. 05), whereas the proportion of correct response times, the proportion of learning times, the levels of miR-137 and Bcl2 protein were lower (P<0. 05). Compared with the Aβ and Aβ+Si-NC groups, the levels of GAS5 mRNA, BAX, caspase-3 protein, neuronal mortality and neuronal apoptosis rate were lower in the Aβ+si-GAS5 and Aβ+si-GAS5+anti miR-NC groups (P<0. 05), whereas the proportion of correct response times, the proportion of learning times, the levels of miR-137 and Bcl2 protein were higher (P<0. 05). In addition, compared with the Aβ+si-GAS5 and Aβ+si-GAS5+anti-miR-NC groups, the levels of GAS5 mRNA, BAX, caspase-3 protein, neuronal mortality, and neuronal apoptosis rate were higher in the Aβ + si-GAS5 + anti-miR-137 group ( P< 0. 05), whereas the proportion of correct response times, the proportion of learning times, the levels of miR-137 and Bcl2 protein were lower (P<0. 05). It was also confirmed that there was a target site between miR-137 and GAS5. Conclusions Interference of GAS5 can upregulate miR-137, thus protecting against Aβ-induced hippocampal neuronal damage and alleviating the process of neuronal apoptosis. In contrast, further downregulation of miR-137 can reverse this process.

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  • Received:October 26,2020
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  • Adopted:
  • Online: October 25,2021
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