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lncRNA ANRIL Ameliorates Oxygen and Glucose Deprivation (OGD) Induced Injury in Neuron Cells via miR-199a-5p/CAV-1 Axis

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Abstract

Ischemia stroke is one of the leading causes of death and disability in the world. Long non-coding RNA ANRIL has been reported to play an important role in ischemic injury. In this study, we aim to explore the mechanism by which ANRIL exhibits protective effect. Middle cerebral artery occlusion mouse models were applied and infarction areas were assessed by TTC assay. The expression of ANRIL and miR-199a-5p were determined by qPCR. Oxygen and glucose deprivation treatment was applied to mimic in vitro ischemia injury in N-2a cells. The levels of BCL-2, BAX, MEK, ERK, CAV-1 were determined by western blot. Cell viability were assessed by MTT assay. The direct interaction among miR-199a-5p and ANRIL, miR-199a-5p and CAV-1 were demonstrated by dual Luciferase report assay. ANRIL and miR-199a-5p expression were changed in both in vivo and in vitro ischemia model. Overexpression of ANRIL or inhibition of miR-199a-5p could protect cells against ischemia induced injury by elevating cell viability through CAV-1 mediated MEK/ERK pathway. miR-199a-5p attenuated CAV-1 expression by direct targeting. ANRIL competitively interacted with miR-199a-5p in N-2a cells, leading to a de-repression of CAV-1. ANRIL protects N-2a cells against ischemia induced injury by elevated CAV-1 by competitively interacting with miR-199a-5p, thus activating MEK/ERK pathway and elevating cell viability.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant No. 81271298).

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Authors and Affiliations

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

    Wei Zhong, Yong-Chang Li, Qian-Yi Huang & Xiang-Qi Tang

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  1. Wei Zhong
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  2. Yong-Chang Li
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  3. Qian-Yi Huang
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Correspondence to Xiang-Qi Tang.

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11064_2019_2951_MOESM1_ESM.tif

Supplementary file 1 Figure S1 Screening of putative ANRIL targeted miRNAs by Luciferase assay in 293t cells. Luciferase activity was detected 48 hours after indicated transfection. F=14.95. Date were shown as Mean ± SD based on three independent experiment. *p < 0.05, **p < 0.01. (TIF 9756 kb)

11064_2019_2951_MOESM2_ESM.tif

Supplementary file 2 Figure S2 Comparison of ANRIL effects in 12 hours and 24 hours OGD-treated N-2a cells. Cell viability of N-2a cells was measured by MTT assay after indicated treatment. F=22.91. Date were shown as Mean ± SD based on three independent experiment. *p < 0.05, **p < 0.01. (TIF 11046 kb)

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Zhong, W., Li, YC., Huang, QY. et al. lncRNA ANRIL Ameliorates Oxygen and Glucose Deprivation (OGD) Induced Injury in Neuron Cells via miR-199a-5p/CAV-1 Axis. Neurochem Res 45, 772–782 (2020). https://doi.org/10.1007/s11064-019-02951-w

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  • DOI: https://doi.org/10.1007/s11064-019-02951-w

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