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Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis

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Abstract

Long noncoding RNA (LncRNA) Peg13 has been demonstrated to protect against neurological diseases. However, its underlying mechanism in the progression of hypoxic-ischemic brain damage (HIBD) has not been well investigated. The expression of target genes was determined in neonatal mice with HIBD and in mouse hippocampal neurons during oxygen–glucose deprivation (OGD) using quantitative real-time PCR (qRT-PCR) and immunoblotting. Functional assays, including CCK-8 cell viability and apoptotic cell detection using TdT mediated dUTP nick ending labeling (TUNEL) assay were used to examine the neuroprotective role of Peg13 in mouse hippocampal neurons. Luciferase assays were performed to determine the regulatory mechanism of Peg13 in OGD-induced neuronal apoptosis. Peg13 was reduced in HIBD mice and OGD-treated mouse hippocampal neurons. Altered Peg13 expression relieved OGD-induced neuronal apoptosis. Mechanistically, Peg13 may serve as a sponge for miR-20a-5p to increase the expression of X chromosome-linked inhibitor of apoptosis (XIAP), a downstream target of miR-20a-5p. Our study showed that Peg13 fulfilled its anti-apoptotic function in neurons through suppressing XIAP expression by sponging miR-20a-5p. Together, Peg13 binds to miR-20a-5p to upregulate XIAP and alleviate HIBD in neonatal mice. The Peg13/miR-20a-5p/XIAP competing endogenous RNA (ceRNA) axis could be a potential therapeutic target for HIBD.

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Authors and Affiliations

  1. Department of Children’s Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Huan Gao, Huijing Xue & Qifei Zhang

  2. Department of Pediatrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangcheng District, Xiangyang, 441000, Hubei, China

    Xiaosan Bing

  3. Department of Ophthalmonogy, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Yue Zhang

  4. Department of Cardiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Yan Zhang

  5. Second Department of Orthopedic Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Yusi Shen

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  1. Huan Gao
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  4. Qifei Zhang
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Correspondence to Xiaosan Bing.

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11064_2021_3474_MOESM1_ESM.jpg

Supplementary file1 (JPG 46 kb) Fig.S1 Schematic diagram showing potential mechanism in which the Peg13/miR-20a-5p/XIAP axis is involved in HIBD. Peg13 sponges miR-20a-5p, reduces inhibition to XIAP, and inhibits mouse hippocampal neuronal apoptosis induced by OGD, which protects against HIBD in neonatal mice.

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Gao, H., Zhang, Y., Xue, H. et al. Long Non-coding RNA Peg13 Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Mice via miR-20a-5p/XIAP Axis. Neurochem Res 47, 656–666 (2022). https://doi.org/10.1007/s11064-021-03474-z

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  • DOI: https://doi.org/10.1007/s11064-021-03474-z

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