Abstract
Alzheimer’s disease (AD) is the most common cause of dementia among older people in worldwide. miR-29c-3p was reported to play a role in AD development. However, the detail function of miR-29c-3p in AD remains unclear. The aim of this research is to analyze the functional mechanism of miR-29c-3p in AD. The RNA levels of miR-29c-3p and Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) were detected by Quantitative real time polymerase chain (qRT-PCR) reaction. Western blot assay was carried out to examine the protein levels of TNFAIP1, Bax, B-cell lymphoma-2 (Bcl-2), Cleaved caspase 3, and Nuclear factor-k-gene binding (NF-κB). The interaction between miR-29c-3p and TNFAIP1 was predicted by online tool TargrtScan and verified using the dual luciferase reporter assay and RNA immunoprecipitation RIP (RIP) assay. Besides, cell proliferation and apoptosis rate were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Aβ treatment decreased miR-29c-3p expression and increased TNFAIP1 expression. Overexpression of miR-29c-3p mitigated the effects of Aβ on proliferation and apoptosis. Similarly, knockdown of TNFAIP1 also reversed the effects of Aβ on cell progression. Interestingly, miR-29c-3p suppressed the expression of TNFAIP1 via binding to 3′UTR of TNFAIP1 mRNA. As expected, overexpression of TNFAIP1 reversed the effects of miR-29c-3p on Aβ-mediated cell progression. Besides, we also confirmed that miR-29c-3p affected Aβ-mediated cell progression by regulating TNFAIP1/NF-κB signaling pathway. In conclusion, our findings confirmed that miR-29c-3p attenuated Aβ-induced neurotoxicity through regulation of NF-κB signaling pathway by directly targeting TNFAIP1, providing the potential value for the treatment of AD patients.
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This work was supported by theHeilongjiang Natural Science Foundation Project (Grant No. H2016101)
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Conceptualization and Methodology: HZ and LS; Formal analysis. Data curation: ZL and KZ; Validation and Investigation: ZL and WL; Writing—original draft preparation and Writing—review and editing: ZL, HZ and LS.
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Liu, Z., Zhang, H., Sun, L. et al. miR-29c-3p Increases Cell Viability and Suppresses Apoptosis by Regulating the TNFAIP1/NF-κB Signaling Pathway via TNFAIP1 in Aβ-Treated Neuroblastoma Cells. Neurochem Res 45, 2375–2384 (2020). https://doi.org/10.1007/s11064-020-03096-x
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DOI: https://doi.org/10.1007/s11064-020-03096-x