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MicroRNA miR-212 regulates PDCD4 to attenuate Aβ25–35-induced neurotoxicity via PI3K/AKT signaling pathway in Alzheimer’s disease

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Abstract

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in the elderly. MicroRNA (miRNA) miR-212-3p (miR-212) has been reported to dysregulated in many neurodegenerative diseases including AD. However, the mechanism and function of miR-212 in AD has not been reported.

Methods

The levels of miR-212 and PDCD4 in AD patients and Aβ25–35-treated SH-SY5Y and IMR-32 cells were measured by qRT-PCR and/or Western blot. The putative target of miR-212 was predicted by DIANA tools online database and the interaction between miR-212 and PDCD4 was validated by dual luciferase reporter assay and RNA pull-down assay. The cell proliferation, cell apoptosis and the protein levels of Bcl-2, Bax, Cleaved caspase 3, p-PI3K, PI3K, p-ATK and ATK were measured by MTT assay, flow cytometry and Western blot.

Results

The level of miR-212 was apparently down-regulated, and the level of PDCD4 was significantly up-regulated in plasma from AD patients and Aβ25–35-treated SH-SY5Y and IMR-32 cells. Following a dual luciferase reporter assay verified the direct interaction between miR-212 and PDCD4. The RNA pull-down assay further validated this interaction. The functional experiment indicated that PDCD4 mitigated the promotion effects on cell viability, the apoptosis-inhibited protein Bcl-2, the ratio of p-PI3K/PI3K, p-ATK/ATK and the suppressive effects on cell apoptosis and the corresponding protein levels of Bax, Cleaved caspase 3 caused by miR-212 mimics.

Conclusion

All the data in this study revealed that miR-212 modulated PDCD4 to regulate cell proliferation, apoptosis through PI3K/AKT signaling pathway in Aβ25–35-treated SH-SY5Y and IMR-32 cells, and this new regulatory network may provide a novel mechanism of AD.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Dalian University Affiliated Xinhua Hospital, Dalian, 116021, China

    Yanjun Wang

  2. Department of Neurology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Rd, Shahekou District, Dalian, 116023, China

    Qing Chang

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  1. Yanjun Wang
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  2. Qing Chang
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Correspondence to Qing Chang.

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Wang, Y., Chang, Q. MicroRNA miR-212 regulates PDCD4 to attenuate Aβ25–35-induced neurotoxicity via PI3K/AKT signaling pathway in Alzheimer’s disease. Biotechnol Lett 42, 1789–1797 (2020). https://doi.org/10.1007/s10529-020-02915-z

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  • DOI: https://doi.org/10.1007/s10529-020-02915-z

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