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LncRNA PVT1 Promotes Neuronal Cell Apoptosis and Neuroinflammation by Regulating miR-488-3p/FOXD3/SCN2A Axis in Epilepsy

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Abstract

It is vital to understand the mechanism of epilepsy onset and development. Dysregulated lncRNAs are closely associated with epilepsy. Our work probed the role of lncRNA PVT1/miR-488-3p/FOXD3/SCN2A axis in epilepsy. The mRNA and protein expressions were assessed using qRT-PCR and western blot. MTT assay and TUNEL staining were conducted to assess cell viability and apoptosis, respectively. TNFα, IL-1β and IL-6 levels were analyzed using ELISA. LDH level was tested by Assay Kit. The binding relationship between PVT1, miR-488-3p and FOXD3 were verified using dual luciferase reporter gene assay. The epilepsy model of rats was established by lithium-pilocarpine injection. Nissl staining was performed to evaluate neuronal damage. PVT1 was markedly upregulated in epilepsy model cells. Knockdown of PVT1 increased the viability, while repressed the apoptosis and inflammatory cytokines secretion as well as LDH level in epilepsy cell model. MiR-488-3p alleviated neuronal injury and neuroinflammation in model cells. MiR-488-3p functioned as the direct target of PVT1, and its inhibition neutralized the effects of PVT1 silencing on neuronal cell injury and neuroinflammation in model cells. Furthermore, miR-488-3p inhibited neuronal cell injury and neuroinflammation in model cells by regulating FOXD3/SCN2A pathway. Finally, animal experiments proved that PVT1 promoted epilepsy-induced neuronal cell injury and neuroinflammation by regulating miR-488-3p-mediated FOXD3/SCN2A pathway. PVT1 promoted neuronal cell injury and inflammatory response in epilepsy via inhibiting miR-488-3p and further regulating FOXD3/SCN2A pathway.

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Data Availability

Enquiries about data availability should be directed to the authors.

Abbreviations

ANOVA:

Analysis of variance

Bax:

Bcl-2-associated X,

Bcl-2:

B-cell lymphoma-2

ceRNA:

Competing endogenous RNA

ELISA:

Enzyme linked immunosorbent assay

FOXD3:

Forkhead box D3

IL:

Interleukin

LDH:

Lactate dehydrogenase

lncRNA:

Long non-coding RNA

miR:

MicroRNA

MTT:

3-(4, 5-Dimethylthiazolyl2)-2, 5-diphenyltetrazolium bromide

PVT1:

Plasmacytoma variant translocation 1

SCN2A:

Sodium voltage-gated channel alpha subunit 2

SD:

Standard deviation

TNF:

Tumor necrosis factor

TUNEL:

TdT-mediated dUTP nick-end labeling

qRT-PCR:

Quantitative real-time polymerase chain reaction

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by the Natural Science Foundation of Hunan Province (Grant No. 2021JJ30961).

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Authors and Affiliations

  1. Department of Neurology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China

    Fang Wen

  2. Department of Neurosurgery, The Second Xiangya Hospital of Central South University, No. 139, Renmin Road, Changsha, 410011, Hunan, People’s Republic of China

    Zhigang Tan, Dezhi Huang, Yugang Jiang & Jun Xiang

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Contributions

FW and JX: wrote the main manuscript text and ZT, DH and YJ: prepared figures. All authors reviewed the manuscript.

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Correspondence to Jun Xiang.

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All authors agree with the presented findings, have contributed to the work, and declare no conflict of interest.

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All animal experimental procedures were reviewed and approved by The Second Xiangya Hospital of Central South University.

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Wen, F., Tan, Z., Huang, D. et al. LncRNA PVT1 Promotes Neuronal Cell Apoptosis and Neuroinflammation by Regulating miR-488-3p/FOXD3/SCN2A Axis in Epilepsy. Neurochem Res 48, 895–908 (2023). https://doi.org/10.1007/s11064-022-03801-y

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