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LncRNA XIST Promoted OGD-Induced Neuronal Injury Through Modulating/miR-455-3p/TIPARP Axis

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Abstract

In recent years, the incidence of ischemic stroke has gradually increased, but its pathogenesis has not been fully elucidated. lncRNAs played an important role in the occurrence and regulation of disease, but the research on ischemic stroke is very limited. Therefore, the role of lncRNA in ischemic stroke needs further exploration. The mice model was built to obtain OGD-induced neuronal cells for the following experiments. The protein expression of TCDD inducible poly [ADP-ribose] polymerase (TIPARP), B-cell lymphoma-2 (Bcl-2) and Cleaved Caspase-3 (Cleaved-cas3) were detected with western blot. qRT-PCR was used to analyze expression of XIST, miR-455-3p and TIPARP. CCK-8 assay indicated the capacity of cell proliferation. Flow cytometry was applied to assess cell apoptosis rate. Moreover, dual-luciferase reporter assay and RIP assay were used to determine that the relationship among XIST, miR-455-3p and TIPARP. In this study, we found that oxygen–glucose deprivation (OGD) induced XIST expression, inhibited miR-455-3p expression and promoted TIPARP mRNA and protein expression in neurons. Furthermore, XIST could affect cell growth of OGD-induced neuronal cells. Further analysis showed that XIST could regulate TIPARP by binding to miR-455-3p, and overexpression of miR-455-3p or inhibition of TIPARP could reverse the effects of high XIST expression on OGD-induced neuronal cells. On the contrary, suppression of miR-455-3p or promotion of TIPARP could reverse the effects of low XIST expression on OGD-induced neuronal cells. XIST could affect cell proliferation and apoptosis through miR-455-3p/TIPARP axis in OGD-induced neuronal cells, providing a new regulatory network to understand the pathogenesis of hypoxia-induced neuronal injury.

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Abbreviations

OGD:

Oxygen–glucose deprivation

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Acknowledgements

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Funding

This work was supported by Wuhan Municipal Health and Family Planning Commission (Grant No. WZ18Q07).

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Correspondence to Lei Li.

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11064_2021_3286_MOESM1_ESM.tif

Supplementary file1 (TIF 203 kb) Supplementary Fig. 1 Effect of XIST on primary cortical neurons cells proliferation and apoptosis. a The expression of XIST was detected in si-NC, si-XIST groups of primary cortical neurons cells using qRT-PCR. b and c Cell viability (b) and cell apoptosis (c) was assessed in Control, OGD, OGD + si-NC and OGD + si-XIST groups of primary cortical neurons cells. Each experiment was repeated three times. *p < 0.05

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Wang, Y., Li, Y., Ma, C. et al. LncRNA XIST Promoted OGD-Induced Neuronal Injury Through Modulating/miR-455-3p/TIPARP Axis. Neurochem Res 46, 1447–1456 (2021). https://doi.org/10.1007/s11064-021-03286-1

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