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LncRNA KCNQ1OT1 Regulates Endoplasmic Reticulum Stress to Affect Cerebral Ischemia-Reperfusion Injury Through Targeting miR-30b/GRP78

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A Correction to this article was published on 10 February 2022

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Abstract

Endoplasmic reticulum stress (ERS) plays an important role in cerebral ischemia-reperfusion injury (CIRI) by regulating apoptosis. Although the role of long non-coding RNA (LncRNA) KCNQ1OT1 in CIRI has been reported, the specific mechanism is still unclear. In this paper, the regulation of ERS by LncRNA KCNQ1OT1 in CIRI and its mechanism were studied. Transient middle cerebral artery occlusion (tMCAO) model was established in SD rats with KCNQ1OT1 intervention. PC12 cells were used to construct the OGD/R cell model. The expressions of LncRNA KCNQ1OT1 and miR-30b were detected by RT-qPCR. TCC staining was used to detect the extent of cerebral ischemia. TUNEL staining was used to detect apoptosis level, and Western blot was used to detect the expressions of ERS and apoptosis-related proteins. The targeted binding of LncRNA KCNQ1OT1, miR-30b, and GRP78 was detected by double luciferase assay. The expressions of LncRNA KCNQ1OT1 and miR-30b were interfered by cell transfection. Cell proliferation was detected by CCK-8. The level of LncRNA KCNQ1OT1 was increased and that of miR-30b was decreased in the blood samples of patients with CIRI. In tMCAO rats with KCNQ1OT1 intervention, the expression of miR-30b was increased, and the ischemic range of brain tissues was decreased. What’s more, the level of ERS was decreased, and the apoptosis of brain tissues was decreased. LncRNA KCNQ1OT1 could regulate miR-30b/GRP78 in OGD/R cells in a targeted way. Intervention of KCNQ1OT1 could promote the proliferation of OGD/R cells, inhibiting the level of ERS and cell apoptosis. Further inhibition of miR-30b could reverse the effect of intervention of KCNQ1OT1. LncRNA KCNQ1OT1 regulates ERS to affect CIRI through targeting miR-30b/GRP78.

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Acknowledgments

The authors would like to thank all members in the Tianjin Medical University General Hospital lab for helpful discussions on the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (81571172).

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Author notes

  1. Yue Li and Ming Yi contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Tianjin Medical University General Hospital, 154 AnShan road, HePing District, Tianjin, 300052, China

    Yue Li, Ming Yi, Qiuxia Zhang, Li Yang & Chunsheng Yang

  2. Department of Clinical Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Dan Wang

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  1. Yue Li
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  2. Ming Yi
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All authors read and approved the final version of the manuscript.

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Correspondence to Chunsheng Yang.

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The study protocol was approved by the Tianjin Medical University General Hospital, and all patients provided written informed consent. All of the procedures were in compliance with The Declaration of Helsinki and relevant policies in China. All animal experiments comply with the ethical requirements of the animal council.

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Li, Y., Yi, M., Wang, D. et al. LncRNA KCNQ1OT1 Regulates Endoplasmic Reticulum Stress to Affect Cerebral Ischemia-Reperfusion Injury Through Targeting miR-30b/GRP78. Inflammation 43, 2264–2275 (2020). https://doi.org/10.1007/s10753-020-01295-w

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