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miR-495 reduces neuronal cell apoptosis and relieves acute spinal cord injury through inhibiting PRDM5

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Abstract

This study aims to investigate the role of miR-495 in neuronal cell apoptosis after acute spinal cord injury (ASCI). The ASCI rat model was established and the Basso, Beattie, and Bresnahan (BBB) score was assessed. miR-495, PR domain containing 5 (PRDM5), and Bcl-2 expressions were measured by qRT-PCR or western blotting. Neuronal cell line PC-12 was subjected to hypoxia condition to simulate the in vitro ASCI model. PC-12 cell apoptosis was measured by flow cytometry, and the interaction between miR-495 and PRDM5 was confirmed by dual luciferase reporter assay. Results showed that BBB score was significantly decreased in ASCI rats compared with sham rats. miR-495 expression was down-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells, and PRDM5 protein level was up-regulated in spinal cord tissue of ASCI rats and hypoxia-induced PC-12 cells. miR-495 overexpression could reduce apoptosis of PC-12 cells, and up-regulated anti-apoptosis protein Bcl-2 protein level. Moreover, PRDM5 was a target of miR-495, and mRNA and protein levels of PRDM5 were negatively regulated by miR-495. miR-495 overexpression could reduce the hypoxia-induced PC-12 cell apoptosis, while PRDM5 overexpression abolished this inhibiting effect. The agomir-495 was injected into ASCI rats, and Bcl-2 protein level and BBB score were increased, but the PRDM5 overexpression reversed these results. Overall, we concluded that miR-495 could inhibit neuronal cell apoptosis and relieve acute spinal cord injury through inhibiting PRDM5.

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  1. Huaihe Hospital of Henan University, 115 **men Street, Kaifeng, 475000, People’s Republic of China

    Yan Zhang, Shanshan Wang, Hongli Li & **a Xu

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  1. Yan Zhang
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  2. Shanshan Wang
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  3. Hongli Li
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  4. **a Xu
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Correspondence to **a Xu.

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10735_2021_9959_MOESM1_ESM.jpg

Supplementary file1 Supplemental Figure 1. a Rat spinal cord tissue was collected, and primary rat neuronal cells, microglia and astrocytes were isolated in sham and ASCI group followed by the protocol of previous study Orre et al. (2014), and the expression of miR-495 was detected by qRT-PCR (n = 7). Rat neuronal cell line PC-12 was cultured without hypoxia, and miR-495 inhibitor was transfected into PC-12 cells. Cells were divided into NC and miR-495 inhibitor group. b The percentage of PC-12 cell apoptosis was determined by Flow cytometry. c Bcl-2 protein level in PC-12 cells was measured by western blotting. The independent experiments were performed for 3 times. **P<0.01, ***P<0.001vs NC or sham. (JPG 841 KB)

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Zhang, Y., Wang, S., Li, H. et al. miR-495 reduces neuronal cell apoptosis and relieves acute spinal cord injury through inhibiting PRDM5. J Mol Histol 52, 385–396 (2021). https://doi.org/10.1007/s10735-021-09959-z

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  • DOI: https://doi.org/10.1007/s10735-021-09959-z

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